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THE  FLUIDS  OF  THE  BODY 


THE  HEETEK  LECTURES 

(NEW  YOEK,    1908) 


ON 


THE  FLUIDS  OF  THE  BODY 


BY 


ERNEST  H.  STARLING,  M.D.,  F.R.O.P.,  F.R.S. 

JODRELL  PROFESSOR  OF  PHYSIOLOGY   IN  UNIVERSITY  COLLEGE,   LONDON 


CHICAGO 
W.    T.    KEENER    AND    COMPANY 
90    WABASH    AYENUE 
1909 


■if  ^ 


BRADBUBY,   AGNEW,    &    CO.   LD.,   PRINTEBS, 
LONDON    AND    TONBBIDGE. 


PEEFACE 

The  first  seven  of  the  Lectures  contained  in  this  volume 
are  based  on  two  courses  of  Lectures  which  I  delivered  at 
University  College,  London,  in  the  summer  of  1907,  and  in 
New  York  during  January,  1908,  at  the  Bellevue  Hospital 
and  Medical  School,  under  the  foundation  of  Dr.  C.  A.  Herter. 
The  eighth  Lecture  represents  one  of  the  Arris  and  Gale 
Lectures  delivered  in  1896  before  the  Eoyal  College  of 
Surgeons  with  certain  additions  and  alterations  necessitated 
by  recent  work  on  the  subject.  I  have  thought  it  advisable 
to  add  this  last  chapter  in  order  that  those,  whose  interests 
lie  chiefly  in  the  practical  treatment  of  disease,  may  appreciate 
how  closely  our  control  of  morbid  processes  is  bound  uj)  with 
the  advance  of  the  purely  physiological  knowledge  which 
forms  the  theme  of  the  first  seven  Lectures. 

I  have  made  no  attempt  to  give  an  exhaustive  account  of 
any  of  the  subjects  treated  in  the  Lectures,  believing  that  a 
jDresentation  from  the  standpoint  of  one  worker  is  more  likely 
to  excite  interest,  whether  of  sympathy  or  dissent.  In  this 
way  my  readers  may  be  stimulated  to  search  out  for  them- 
selves, in  the  wards  or  in  the  laboratory,  the  answers  to  some 
of  the  riddles  with  which  they  are  here  confronted. 


EENEST   H.    STARLING. 


40,  West  End  Lane,  N.W., 
January  J  1909. 


CONTENTS 


LECTUEE  I 
THE   PHYSICAL   PKOPERTIES   OF   PROTOPLASM  .  .  .  1 — 26 

LECTUEE  n 
THE   OSMOTIC   RELATIONSHIPS   OF  CELLS  .  .  .         27 — 40 

LECTUEE  ni 
THE   INTAKE   OF   FLUID 41 — 61 

LECTUEE  IV 

THE   EXCHANGE   OF   FLUIDS   IN   THE  BODY — THE  PRODUC- 
TION  OF   LYMPH Q2 — 87 

LECTUEE  V 
THE   ABSORPTION   OF   THE   INTERSTITIAL   FLUIDS      .  .         88 — 103 

LECTUEE  YI 
THE   OUTPUT   OF   FLUID 104 — 133 


Vlll  CONTENTS 

LECTUEE  VII 

THE  FLUID  BALANCE  OF  THE  BODY    .     .     .     .   134 155 

LECTUEE  YIII 
THE  CAUSATION  OF  DROPSY 156 177 


INDEX 279 


THE  FLUIDS  OF  THE  BODY 

LECTURE   I 

PHYSICAL  PROPERTIES  OF  PROTOPLASM 

In  all  living  organisms,  whether  belonging  to  the  animal 
or  vegetable  kingdom,  the  presence  of  water  as  an  integral 
part  of  their  structm*e  seems  to  be  essential  for  the  manifesta- 
tion of  any  vital  phenomenon. 

It  is  a  familiar  fact  that  the  activity  of  even  the  lowest 
forms  of  life  cannot  be  displayed  in  the  absence  of  this  sub- 
stance. Highly  unstable  materials,  such  as  dead  tissues  of 
animals  themselves,  if  thoroughly  dried  can  be  kept  indefinitely 
without  the  slightest  sign  of  putrefaction.  Access  of  water  to 
such  material  at  once  creates  the  conditions  suitable  for  the 
growth  of  the  micro-organisms  which  bring  about  putrefac- 
tion. Vegetable  seeds  undergo  no  change  until  moistened ; 
when,  almost  immediately,  commences  the  w^onderful  series  of 
chemical  changes  which  culminate  in  the  germination  of  the 
seed  and  the  production  of  a  new  individual. 

When  we  call  to  mind  the  fact  that,  at  the  time  that  life  was 
coming  into  being  on  the  earth's  surface,  w^ater  was  every- 
where present,  it  is  not  surprising  that  it  should  have  played 
a  part  in  the  formation  of  the  complex  self-polymerising 
material  which  formed  the  primitive  protoplasm.  If  we  take 
the  unique  properties  of  water  into  consideration — its  fluid 
character,  its  high  specific  heat,  its  solvent  powers  (which  are 

F.B.  B 


'J  THE    FLUIDS    OF    THE    BODY 

unequalled  by  that  of  any  other  liquid),  its  ionising  power 
over  salts,  we  see  that,  having  once  entered  into  the  com- 
position of  protoplasm,  it  must  determine  many  of  the  qualities 
of  this  material  and  play  an  important  part  in  all  the  chemical 
and  physical  changes  which  make  up  what  we  call  life. 
Protoplasm  must  be  regarded  as  a  fluid  and  as  consisting  of  a 
solution  or  suspension  in  water  of  compounds  of  very  varying 
complexity.  It  follows  that  all  the  energies  which  are  dis- 
played by  the  living  cell  must  be  derived  from  the  energies 
of  substances  in  solution,  and  must  therefore  be  derivable 
from  and  measurable  in  terms  of  osmotic  energy,  when  taking 
place  in  the  interior  of  the  cell ;  of  surface  energy,  when 
occurring  at  the  dividing  surface  between  the  living  cell  and 
its  environment. 

To  these  two  modes  of  energy  we  must  ultimately  be  able 
to  refer  all  the  manifestations  of  life.  No  substance  can 
obtain  entrance  into  a  living  organism,  except  it  be  soluble. 
Until  solution  occurs,  particles  of  food,  mechanically  intro- 
duced into  the  cell  protoplasm,  take  no  part  in  the  cycle 
of  processes  which  make  up  the  life  of  the  cell.  All 
the  chemical  changes,  which  we  have  to  study  under  the 
heading  of  metabolism,  relate  to  changes  in  and  between 
substances  in  solution.  It  is  a  common  practice  to  speak 
of  the  energy  of  the  body  as  derived  from  the  combustion  of 
the  foodstuffs.  The  statement  is  a  little  dangerous  if  it  brings 
too  strongly  to  our  minds  the  image  of  burning  coal  or  other 
combustible  material,  and  makes  us  forget  that  the  processes 
of  oxidation,  which  are  responsible  for  the  production  of 
energy  in  the  body  and  give  rise  to  the  same  end-products 
as  would  the  combustion  of  foodstuffs  outside  the  body,  i.e. 
CO2  and  H2O,  really  occur  by  continual  gradations,  the  oxygen 
and  the  oxydate  in  every  case  being  dissolved  in  a  watery 
menstruum. 


PHYSICAL  PROPERTIES  OF  PROTOPLASM  6 

The  available  energy  of  a  living  cell  at  any  given  moment 
may  be  regarded  as  made  up  of  two  factors,  viz. : 

A.  The  total  osmotic  pressure  of  all  the  dissolved  substances 
present  in  the  cell. 

B.  The  chemical  energy  of  these  substances ;  i.e.,  the  total 
energy,  which  will  be  produced  when  they  undergo  complete 
oxidation. 

One  might  speak  of  these  two  factors  as  the  kinetic  or  actual, 
and  the  potential  (osmotic)  energy  of  the  cell. 

Since  the  actual  energy  of  the  cell  is  represented  by  the 
osmotic  pressure  of  its  dissolved  molecules,  and  therefore 
depends  on  the  total  number  of  the  molecules  present,  the 
molecular  concentration  of  the  dissolved  substances  in  the 
fluid  pervading  the  cell  becomes  a  matter  of  great  importance. 
Everyone  is  familiar  with  the  fact  that,  for  the  preservation  of 
isolated  cells,  it  is  essential  to  keep  them  in  some  fluid,  which 
we  designate  as  normal.  This  term  being  interpreted  signifies 
merely  that  our  normal  fluid  must  have  a  certain  molecular 
concentration.  If  it  be  hypertonic  or  hypotonic,  we  know 
that  the  cell  shrivels,  or  swells  up  and  bursts,  as  the  case  may 
be.  Whereas  the  actual  energy  of  any  cell  is  determined 
solely  by  its  molecular  concentration  at  the  moment,  its 
potential  energy  depends  on  the  nature  even  more  than  on  the 
amount  of  the  substances  which  are  present  in  solution. 
According  to  the  nature  of  these  substances,  so  the  reactions 
and  the  behaviour  of  the  cell  will  differ.  Diversity  of  func- 
tion implies  diversity  of  structure  and  composition. 

Although  every  active  cell  is  constantly  taking  up  and  giving 
out  dissolved  substances  to  the  surrounding  medium,  and 
although  in  almost  every  case  its  external  surface  is  freely 
permeable  to  water,  in  no  case  do  the  inorganic  salts  of 
a  living  cell  bear  any  relation  to  those  of  its  environ- 
ment.    Thus,   even  if   we  take  such  inert  structures  as  the 

b2 


4  THE    FLUIDS    OP    THE    BODY 

red  blood- corpuscles,  we  find  a  striking  difference  between 
their  contained  salts  and  those  of  the  surrounding  blood- 
serum.  These  differences  are  well  shown  in  the  following 
Table. 

Inorganic  Constituents  of  Corpuscles  and  Serum  of 
Pig  in  1,000  Parts  (Bunge). 


Inorganic 
Substances. 

Corpuscles. 

Serum. 

Total 

8-9 

7-7 

K2O 

* 
o'543 

0-273 

NaaO 

0 

4-272 

CaO 

0 

0-136 

MgO 

0-158 

0-038 

CI 

1-504 

3-611 

P2O5 

2-067 

0-188 

The  same  individual  divergencies  are  found  if  we  analyse  a 
number  of  seaweeds  from  the  same  locality,  all  therefore 
bathed  by  the  same  sea-water.  The  following  Table  (page  5) 
shows  the  percentage  composition  of  the  ash  of  four  different 
kinds  of  fucus  growing  in  close  proximity  to  one  another  at 
the  mouth  of  the  Clyde.* 

We  see  that  a  living  cell,  though  in  constant  osmotic  inter- 
change both  of  water  and  dissolved  substances  with  its 
surroundings,  nevertheless  possesses  a  composition  widely 
differing  from  that  of  the  latter  and  determined  chiefly  by  the 
nature  and  function,  i.e.,  by  the  hereditary  disposition  of  the 
cell  itself.      Is  it  possible  to  find  in  the  physical  structure  or 

*  E.  Overton,  "  Ueber  den  Mechanismus  der  Eesorption  und  der 
Sekretion."  Nagel's  "  Handbuch  d.  Physiol,  d.  Menschen."  Bd.  II. 
2te  Hefte.     1906-7. 


PHYSICAL   PROPERTIES    OF    PROTOPLASM  5 

chemical  composition  of  the  material  out  of  which  the  cell  is 
built  up  any  clue  to  the  explanation  of  its  behaviour  ? 

An  isolated  living  cell,  when  viewed  under  the  microscope, 
appears  as  a  translucent  mass,  in  which,  in  some  cases,  very 
Httle  trace  of  structural  differentiation  is  to  be  seen.  In  other 
cells  we  make  out  such  structures  as  a  nucleus,  contractile 


— 

Fucus  cli;,Mtatus. 

F.  vesiculosus. 

F.  nodosiis. 

F.  serratus. 

K 

22-40 

15-23 

10-07 

4-51 

Na 

8-29 

11-16 

15-80 

21-15 

Ca 

11-86 

9-78 

12-80 

16-36 

Mg 

7-44 

7-16 

10-93 

12-66 

Fe203 

0-62 

0-33 

0-29 

0-34 

NaCl 

28-39 

25-10 

2016 

18-76 

Nal 

3-62 

0-37 

0-54 

1-33 

SO3 

13-26 

28-16 

26-69 

21-06 

P2O5 

2-56 

1-36 

1-52 

4-40 

Si02 

1-56 

1-35 

1-20 

0-43 

Total     ash     (per 
cent,    of    dried 
plant) 

20-04 

16-39 

16-19 

15-63 

vacuoles,  permanent  cavities  or  openings,  such  as  the  mouth, 
and  structures  attached  to  the  surface,  such  as  cilia.  In  every 
case  the  jelly-like  mass  has  a  well-defined  border  or  line 
of  demarcation  between  it  and  the  circumambient  medium. 

On  treating  the  cell  in  various  ways,  as,  e.g.,  by  the  use  of 
fixing  reagents  and  dye-stuffs,  we  learn  the  existence  of 
differentiation,  physical  as  well  as  chemical,  within  the  minute 
limits  of  the  cell.  Apart  from  the  cell  organs,  such  as  nucleus  or 
vacuole,  we  find  in  most  cases  that  the  cytoplasm,  which  forms 


6  THE    FLUIDS    OF    THE    BODY 

the  main  substance  of  the  cell  itself,  reveals  signs  of  differentia- 
tion and  betrays  a  reticular,  or  honeycomb,  structure.  How 
far  such  a  structure  is  an  artefact  and  depends  on  the  action 
of  reagents  on  a  homogeneous  material  is  still  a  matter  of 
discussion.  When  a  cell,  such  as  the  ovum,  accumulates  food 
supi^lies,  its  natural  tendency  is  to  deposit  these  materials 
in  alveoli  within  the  protoplasm,  so  that  the  whole  structure 
acquires  an  alveolar  arrangement  which  is  visible  in  the  fresh 
living  protoplasm.  Although  the  margin  of  a  cell  is  structurally 
defined,  and  although  in  many  cases  a  cell  presents  a  form  and 
shape  which  is  characteristic,  it  is  impossible  to  regard  the 
protoplasm  of  which  it  is  composed  as  a  solid.  The  existence 
of  active  streaming  movements,  which  may  occur  in  opposite 
directions  within  the  limits  of  a  thin  strand  of  protoplasm, 
e.ff.,  in  Chara,  shows  that  the  substance,  out  of  which  the  cell 
is  built,  is  fluid — fluid  of  varying  degrees  of  viscosity  in  different 
cells,  or  in  different  parts  of  one  and  the  same  cell. 

The  fact  that  a  cell  may  have  a  distinct  shape  and  a  resist- 
ance to  deformation  may  be  due  to  the  surface  tension 
existing  between  the  cell  and  its  surroundings,  or  between 
different  parts  of  the  cell.  A  globule  of  mercury,  though 
perfectly  fluid,  presents  resistance  to  deformation  and  recovers 
its  shape  with  a  certain  degree  of  energy  after  any  deforming 
force  has  been  applied.  By  multiplying  surfaces  within  a 
fluid  it  is  possible  to  rob  the  whole  mass  of  most  of  the 
properties  which  we  regard  as  characteristic  of  fluid.  Thus 
by  the  addition  of  a  little  albumen  to  petroleum  and  agitation 
so  as  to  break  up  the  petroleum  into  droplets,  each  surrounded 
by  a  layer  of  the  albuminous  fluid,  it  is  possible  to  turn  this 
liquid  into  a  material  which  can  be  handled  with  a  shovel. 
Our  histological  experience  would  therefore  point  to  proto- 
plasm being  built  up  of  fluid  of  varying  consistencies  and 
qualities  which  may  still  possess  the  property  of  flowing  freely 


PHYSICAL  PROPERTIES  OF  PROTOPLASM  7 

like  a  fluid,  or  have  a  distinct  form  impressed  upon  it  in  virtue 
of  the  surface  tension  between  the  cell  and  its  surrounding 
medium,  or  between  different  parts  of  the  interior  of  the  cell. 

When  we  enquire  into  the  physical  conditions  which  deter- 
mine the  histological  characters  and  behaviour  of  living  cells, 
the  first  fact  which  we  have  to  take  into  account  is  that 
the  cell  and  all  its  parts  are  made  up  of  colloids.  Every 
chemical  or  physical  change  which  occurs  within  a  cell  must 
therefore  be  a  change  affecting  colloids  and  take  place 
in  a  colloidal  medium.  Without  some  understanding  of  the 
behaviour  of  this  kind  of  material,  it  is  impossible  even  to 
make  a  beginning  in  our  task  of  referring  vital  phenomena  to 
their  causal  events,  or  of  tracing  out  the  chain  of  processes 
intervening  between  the  occurrence  of  a  physical  change  in 
the  environment  of  the  organism  and  the  physiological  change 
in  the  organism  itself  which  is  its  reaction  to  stimulus  and  the 
necessary  condition  of  its  continued  existence. 

The  term  colloid  was  first  introduced  by  Graham,  Professor 
of  Chemistry  in  University  College,  London,  to  denote  a  class 
of  bodies  of  which  gum,  dextrin,  albumen  and  gelatin  may 
serve  as  types.  They  are  distinguished  in  many  respects  from 
substances  such  as  salts,  most  of  which  can  be  easily  obtained 
in  crystalline  form  and  are  therefore  designated  crystalloids. 

These  colloids  were  shown  by  Graham  to  occur  in  two 
forms — either  in  a  state  of  solution  or  pseudo-solution,  which 
he  designated  as  a  Sol  (hydro-sol,  alco-sol,  etc.,  according  to 
the  nature  of  the  solvent),  and  in  a  solid  form  as  a  Gel.  In 
this  latter  condition  (a  familiar  example  of  which  is  gelatin 
below  a  certain  temperature)  the  substance  is  associated,  as  in 
the  sol,  with  a  fluid  such  as  water  or  alcohol ;  the  substance 
plus  solvent  form  however  a  mass  apparently  homogeneous, 
which  is  solid  and  has  rigidity  and  elasticity. 

In  many  cases  the  gel  can   be  converted  into  a  sol   and 


8  THE    FLUIDS    OF    THE    BODY 

vice  versa  by  the  alteration  of  external  conditions.  In  other 
cases  the  change  is  irreversible  and  the  gel  once  formed  from 
a  sol  cannot  be  brought  again  into  the  fluid  form. 

Other  characteristics  of  colloids  are  their  extremely  slight 
diffusibility  and  the  fact  that  they  are  practically  indiffusible 
through  animal  membranes.  This  latter  property  was  utilised 
by  Graham  in  the  invention  of  the  process  of  dialysis  for 
freeing  colloidal  solutions  from  dissolved  salts.  Many  of 
these  properties  suggest  that  the  characteristics  of  colloids 
may  be  bound  up  with  the  large  size  of  their  molecules. 
Thus  it  is  often  found  that,  whereas  the  lower  members  of  an 
organic  series  fall  into  the  class  of  crystalloids,  the  higher 
members  of  the  same  series  are  typical  colloids.  Sodium 
acetate,  for  instance,  with  a  low  molecular  weight,  is  soluble  in 
water  and  diffuses  with  ease ;  sodium  palmitate,  with  a  mole- 
cule many  times  the  size  of  the  acetate,  is  soluble  in  water,  but 
the  solution  so  formed  is  colloidal.  The  soap  itself  is  practi- 
cally indiffusible,  and  when  a  solution  either  in  water  or  alcohol 
is  cooled,  we  get  a  gel  similar  to  that  formed  on  cooling  a 
solution  of  gelatin.  Nor  does  the  existence  of  such  simple 
bodies  as  silicic  acid,  ferric  hydrate,  or  even  metals  themselves 
in  the  form  of  colloidal  solution,  militate  against  this  con- 
clusion, since  we  have  every  reason  to  believe  that,  in  the 
colloidal  state,  the  molecules  of  ferric  oxide  or  silicic  acid  are 
no  longer  present  as  Si02  or  re203,  but  as  highly  polymerised 
aggregates  of  molecules  of  the  simpler  type. 

All  the  methods,  which  are  at  our  disposal  for  determining 
the  number  of  molecules  in  a  solution,  point  to  this  number, 
in  the  case  of  the  colloid  solution  of  ferric  hydrate,  being 
many  hundred  times  smaller  than  would  be  the  case  if  the 
solution  contained  molecules  of  FcaOa  or  re2(OH)6.  It  is 
therefore  not  surprising,  in  view  of  the  results  of  chemical 
examination  of  living  structures,  that  the  material  of  which 


PHYSICAL  PROPERTIES  OF  PROTOPLASM  9 

these  are  built  up  should  be  almost  exclusively  colloidal  in 
nature.  "When  we  take  protoplasm,  i.e.,  living  material  such 
as  would  be  presented  by  the  pseudopodium  of  myxomy- 
cetes,  by  lymph  cells,  or  by  liver  cells,  and  break  it  up  by 
chemical  means  so  as  to  arrive  at  an  idea  of  its  proxi- 
mate constituents,  the  first  fact  which  impresses  us  is  the 
enormous  complexity  of  its  chemical  structure.  As  proxi- 
mate constituents  of  living  tissues  we  are  accustomed  to 
name  the  proteins,  the  fats,  and  the  carbohydrates.  The 
proteins,  which  are  gradually  yielding  up  the  secret  of  their 
composition  in  the  hands  of  accomplished  chemists,  such  as 
Fischer,  Kossel,  and  others,  are  losing  in  the  process  nothing 
of  their  imagined  complexity. 

In  the  living  cell,  as  has  been  pointed  out  by  Kossel,  the 
proteins  rarely  occur  in  the  uncombined  condition.  In  almost 
all  cases  they  are  associated  with  other  complex  molecules 
such  as  nuclein,  with  phosphorised  fats  such  as  lecithin,  and 
with  carbohydrates  or  nitrogen-containing  derivatives  of 
the  carbohydrates.  In  the  case  of  one  protein,  viz.,  haemo- 
globin, many  lines  of  research  concur  in  pointing  to  a 
molecular  weight  in  the  neighbourhood  of  16,000.  A  direct 
determination  of  the  osmotic  pressure  of  the  proteins  of  serum 
points  to  a  molecular  weight  of  about  30,000,  and  it  seems  there- 
fore probable  that  the  highly  complex  compound  of  nuclein, 
lecithin,  fat,  carbohydrates  and  protein,  which  form  the  main 
constituents  of  the  cytoplasm,  may  have  a  molecular  weight 
well  over  100,000.     ' 

The  size  of  a  molecule  of  water  has  been  reckoned  to  be 
about  '7  X  10  "^  mm.  If  the  molecular  diameter  were  propor- 
tional to  the  molecular  weight,  a  molecule  ten  thousand  times 
as  large,  i.e.,  with  a  molecular  weight  of  180,000,  would  have 
a  diameter  of  '7  X  10"^  mm.  This  is  0"7  ju,  i.e.,  a  size  within, 
the  limits  of  microscopic  vision  and  transcending  the  particles 


10  THE    FLUIDS    OF    THE    BODY 

of  many  permanent  suspensions.  Although  we  have  no 
evidence  that  the  size  of  a  molecule  is  arithmetically  propor- 
tional to  its  molecular  weight,  there  is  no  doubt  that  the  size 
must  be  a  function  of  the  molecular  weight  and  must  increase 
with  the  latter.  A  molecule  with  a  molecular  weight  of 
100,000,  although  probably  not  directly  visible  with  the  micro- 
scope, might  have  a  refractive  index  differing  from  the 
surrounding  medium  ;  like  a  particle  of  dust  in  the  familiar 
Tyndall  experiment  it  would  scatter  rays  of  light,  and  might 
therefore  be  rendered  visible  by  some  method  of  illumination 
such  as  that  adopted  in  the  ultra-microscope  of  Zigmondy. 
But  such  huge  molecules  can  no  longer  be  expected  to  follow 
exactly  the  laws  which  have  been  derived  from  the  study 
of  the  behaviour  of  the  almost  perfect  gases  and  similar 
substances.  In  these  the  size  of  a  molecule  under  ordinary 
conditions  is  negligible  compared  with  the  distance  between 
each  molecule,  so  that  each  molecule  may  be  regarded  as 
a  point  of  force.  Molecules  of  the  size  we  have  suggested 
would  possess  the  properties  of  matter  in  mass.  They  would 
have  a  surface  of  measurable  extent,  and  their  relation  to  the 
molecules  of  the  Vv^ater,  or  solvent  surrounding  them,  would 
l)e  determined  by  the  laws  of  adsorption  rather  than  by  the 
laws  of  interaction  of  molecules.  As  a  matter  of  fact  we  find 
that  the  solutions  of  the  different  colloids  which  make  up  the 
animal  cell  present  an  amazing  mixture  of  properties,  some 
of  which  betray  them  as  mechanical  suspensions,  while  others 
partake  of  the  nature  of  chemical  reactions,  such  as  those 
usually  dealt  with  by  the  chemist. 

Let  us  briefly  consider  some  of  the  distinguishing  features 
of  such  solutions.  It  has  been  hotly  debated  whether  a 
colloidal  solution,  or  sol,  is  to  be  regarded  as  a  solution  at 
all,  or  as  a  suspension.  The  chief  criterion  of  a  true  solution 
is  its  homogeneity.     In  a  solution  the  molecules  of  the  solute 


PHYSICAL  PROPERTIES  OF  PROTOPLASM  11 

are  equally  diffused  throughout  the  molecules  of  the  solvent, 
and  it  is  impossible  without  the  application  of  energy  to 
separate  one  from  the  other.  Thus  filtration,  gravitation, 
leave  the  composition  of  the  sohition  unchanged.  It  is  true 
that  by  the  employment  of  certain  kinds  of  membrane, 
e.fj.,  the  semi-permeable  copper  ferrocyanide  membrane,  it  is 
possible  to  separate  solute  from  solvent,  but  in  this  case  the 
force  required  to  effect  the  filtration  is  enormous  and  grows 
with  every  increase  in  the  strength  of  the  solution.  The 
increase  of  the  force  required  is  the  osmotic  pressure  of  the 
solution,  and  it  becomes  natural  therefore  to  regard  the  posses- 
sion of  an  osmotic  pressure  as  a  distinguishing  criterion  of 
a  true  solution.  Is  there  any  evidence  that  colloid  solutions 
also  disj^lay  an  osmotic  pressure  ?  Sabanejeff  attempted  to 
decide  this  question  in  an  indirect  manner,  i.e.,  by  the  deter- 
mination of  the  depression  of  freezing-point  caused  by  the 
addition  to  water  of  various  colloids.  The  depressions 
observed  by  this  author  were  so  small  that  they  might  be 
regarded  as  falling  within  the  limits  of  experimental  error. 
Assuming  that  the  depression  in  each  case  was  due  to  the 
presence  of  the  dissolved  colloid,  Sabanejeff  arrived  at  the 
following  molecular  weights  for  certain  colloids : — 

Tannin         1,322 

Egg  albumen          .  .          . .          . .  15,000 

Starch           over  30,000 

Silicic  acid  .  .          . .  over  49,000 

I  have  attempted  to  determine  the  osmotic  pressure  of 
colloidal  solutions  directly,  taking  advantage  of  the  fact  that 
many  colloidal  membranes,  while  permitting  the  passage 
of  water  and  salts,  are  impermeable  to  colloids  in  solution. 

In  order  to  determine  the  osmotic  pressure  of  the  serum 
proteins,  150  cc.  of  clear  filtered  serum  are  filtered  under  a 
pressure  of  30  to  40  atmospheres  through  a  porous  cell  which 


12 


THE    FLUIDS    OF    THE    BODY 


has  been  previously  soaked  with  gelatin.  At  the  end  of 
twenty-four  hours  about  75  cc.  of  a  clear,  colourless  filtrate 
is  obtained  perfectly  free  from  all  traces  of  protein.  This 
filtrate  has  practically  the  same  freezing  point  as  the  original 
serum,  provided  that  the  first  ten  cubic  centimetres  of  the 
filtrate,  which  are  contaminated  with  the  water  permeating 
the  gelatin,*  have  been  discarded.  Of  course  the  proteins  con- 
tained in  the  serum,  if  they  have  an  osmotic  pressure,  must 


cause  some  depression  of  the  freezing  point,  but  a  pressure  of 
45  mm.  Hg.  would  correspond  only  to  '005  C,  which  is  within 
the  error  of  observation.  The  concentrated  serum  left  behind 
in  the  filter  is  then  put  into  the  osmometer,  the  filtrate  being 
used  as  the  inner  fluid. 

The  construction  of  the  osmometer  will  be  readily  seen  from 
the  accompanying  diagram. 

The  tube  BB  is  made  of  silver  gauze  connected  at  each  end 
to  a  tube  of  solid  silver.     Piound  the  gauze  is  wrapped  a  piece 


*  The  first  portion  of  the  filtrate  would  be  more  dilute  than  the  later 
portions  owing  to  the  adsorption  of  some  of  its  salts  by  the  gelatin  film. 


PHYSICAL    PROPERTIES    OF    PROTOPLASM  13 

of  peritoneal  membrane  (as  in  making  a  cigarette).  This  is 
painted  all  over  with  a  solution  of  gelatin  (10  per  cent.),  and 
then  a  second  layer  of  membrane  applied.  Fine  thread  is  now 
twisted  many  times  round  the  tube  to  prevent  any  disturbance 
of  the  membranes,  and  the  whole  tube  is  soaked  for  half- 
an-hour  in  a  warm  solution  of  gelatin.  In  this  way  one 
obtains  an  even  layer  of  gelatin  between  two  layers  of  peritoneal 
membrane,  and  supported  by  the  wire  gauze.  This  tube  so 
prepared  is  placed  within  a  wide  tube  AA  which  is  provided 
with  two  tubules  at  the  top.  One  of  these  0  is  for  filling  the 
outer  tube,  the  other  is  fitted  with  a  mercurial  manometer  M. 
Two  small  reservoirs  CC  are  connected  with  the  outer  ends  of 
BB  by  means  of  rubber  tubes.  The  whole  apparatus  is  placed 
in  a  wooden  cradle  DD  pivoted  at  X  and  provided  with 
a  cover,  so  that  it  may  be  filled  with  fluids  at  different  tem- 
peratures if  necfessary.  The  colloid  solution  is  placed  in  AA, 
and  the  reservoirs  CC  and  inner  tube  BB  are  filled  with  a  salt 
solution  approximately  or  absolutely  isotonic  with  the  colloid 
solution.  The  apparatus  is  then  made  to  rock  continuously 
for  days  or  weeks  by  means  of  a  water  motor.  (The  two 
reservoirs  CC  are  corked,  and  connected  by  means  of  a  tube, 
in  order  to  avoid  evaporation.)  In  this  way  the  fluid  on  the 
two  sides  of  the  membrane  is  continually  renewed,  and  the 
attainment  of  an  osmotic  equilibrium  facilitated.* 

With  this  apparatus  I  found  that  the  colloids  in  blood 
serum,  containing  from  6  to  8  per  cent,  proteins,  had  an 
osmotic  pressure  of  25  to  30  mm.  Hg.,  which  would  correspond 
to  a  molecular  weight  of  about  30,000.  Using  "  purified  " 
proteins,  Waymouth  Eeid  f  was  unable  to  detect  any  osmotic 

''■  A  more  compact  osmometer  for  similar  purposes  has  been  devised  by 
Moore,  and  will  be  found  described  in  tbe  Biochemical  Journal,  II.,  54, 
1906. 

t  Jourii.  of  Physiol,  Yol.  XXXL,  p.  438,  1904. 


14  THE    FLUIDS    OF    THE    BODY 

pressure  whatever,  though  haemoglobin*  gave  a  small 
osmotic  i:)ressure  of  about  4  mm.  Hg.  for  a  1  per  cent, 
solution.  More  satisfactory  results  were  obtained  by  Hiifner 
and  Gausser.j  A  5*27  per  cent,  solution  of  horse  haemo- 
globin gave  a  pressure  of  58  mm.  Hg.  and  a  10'8  per  cent, 
solution  haemoglobin  from  the  ox  gave  a  pressure  of  109  mm. 
Hg.  at  10°  C,  corresponding  to  a  molecular  weight  of  16,000. 
Moore  has  found  that  soaps  exercise  a  feeble  osmotic  j)ressure. 
Certain  colloidal  solutions,  such  as  starch  or  glycogen,  and 
probably  globulin,  display  no  appreciable  osmotic  pressure. 
We  must  conclude  that,  in  a  hydrosol,  the  osmotic  pressure 
is  only  small  and  may  be  entirely  absent.  Can  we  there- 
fore divide  colloidal  solutions  into  two  classes,  viz.,  those 
which  form  true  solutions  and  present  a  feeble  osmotic 
pressure,  and  those  which  only  form  suspensions  and  therefore 
exert  no  osmotic  j)ressure  ?  A  consideration  of  the  behaviour 
of  various  colloidal  solutions  shows  that  such  a  division  is  not 
possible.  In  the  case  of  inorganic  colloids,  such  as  arsenious 
sulphide,  Picton  and  Linder  have  pointed  out  that  all  grades 
exist  between  true  solutions  and  suspensions.  With  increas- 
ing aggregation  of  the  molecules,  the  suspension  becomes 
coarser  and  coarser  until  finally  the  sulphide  separates  in  the 
form  of  a  precipitate. 

Moreover,  all  colloids,  even  those  such  as  starch  or  gelatin, 
which  are  insoluble  in  cold  water,  exhibit  a  phenomenon,  viz. : 
Quellung  or  imbibition,  which  in  many  cases  it  is  impossible 
to  distinguish  from  the  process  of  solution.  This  phenomenon, 
which  was  long  ago  studied  by  Chevreul  and  has  lately  been 
the  subject  of  a  series  of  careful  experiments  by  Overton,  is 
exhibited  by  all  animal  tissues  and  all  colloids.  Thus  elastic 
tissue   dried  in  vacuo  absorbs   from  a  saturated   solution   of 


-  W.  Eeid,  Journ.  of  Physiol,  Vol.  XXXIII.,  pp.  12—19. 
t  Du  Lois'  Arc/dv,  1907,  p.  209. 


PHYSICAL    PROPERTIES    OF    PROTOPLASM  15 

common  salt  36*8  per  cent,  of  water  and  salt.  If  dried  colloids 
be  suspended  in  a  closed  vessel  over  various  solutions,  they 
will  take  up  water  in  the  form  of  vapour  from  the  solution, 
and  the  osmotic  pressure  of  the  solution  in  question  will 
inform  us  as  to  the  amount  of  work  which  would  be  necessary 
in  order  to  separate  the  water  again  from  the  colloids.* 

Thus  it  has  been  reckoned  that  to  press  out  water  from 
gelatin  containing  28*4  parts  of  water  to  100  parts  of  dried 
gelatin  would  require  a  pressure  of  over  two  hundred  atmo- 
spheres. The  imbibition  pressure  of  colloids  increases  rapidly 
with  the  concentration  of  the  colloid  and  at  a  greater  rate 
than  the  latter.  In  this  respect  however,  imbibition  pressure 
resembles  osmotic  or  indeed  gaseous  pressure.  At  extreme 
pressures  the  pressure  of  hydrogen  rises  more  rapidly  than 
its  volume  diminishes.  In  solutions  this  effect  is  more 
marked  the  larger  the  size  of  the  molecule.  Thus  a  6'7 
per  cent,  solution  of  cane  sugar  has  the  same  vapour  tension, 
and  therefore  the  same  osmotic  pressure,  as  a  "67  per  cent. 
NaCl  solution.  A  67  per  cent,  cane  sugar  solution  has  how- 
ever the  same  osmotic  pressure  as  an  18J  per  cent,  solution  of 
common  salt.  It  is  impossible  therefore  to  draw  any  hard 
line  of  distinction  between  imbibition  pressure  and  osmotic 
pressure.  In  the  same  way  it  is  impossible  to  say  where  a 
fluid  ceases  to  be  a  solution  and  becomes  a  suspension.  All 
grades  are  to  be  found  between  a  solution  such  as  that  of 
common  salt  with  a  high  osmotic  pressure  and  optical  homo- 
geneity, and  a  solution  such  as  that  of  starch,  which  scatters 
incident  light  and  is  therefore  opalescent  and  in  ordinary 
solution  has  no  measurable  osmotic  pressure. 

The  close  connection  between  the  processes  of  imbibition 
and  of  solution  is  shown  also  by  the  fact  that  this  latter  process 

*  Cp.  Overton,  loc.  cit.,  p.  796. 


16  THE    FLUIDS    OF    THE    BODY 

occurs  only  in  certain  media,  the  nature  of  the  media  being 
dependent  on  the  chemical  character  of  the  substances  in 
question.  Thus  all  the  crystalline  carbohydrates — such  as 
grajDe  sugar  and  cane  sugar — are  easily  soluble  in  water, 
only  slightly  soluble  in  alcohol,  and  practically  insoluble  in 
ether  and  benzol.  The  amorphous  carbohydrates,  which  must 
be  regarded  as  derived  by  a  process  of  condensation  from  the 
crystalline  carbohydrates,  e.g.,  starch,  cellulose,  gum  arable, 
etc.,  have  a  strong  power  of  imbibition  for  water.  This  power 
may  be  limited,  as  in  the  case  of  cellulose,  or  may  be  unlimited, 
as  in  the  case  of  gum  arable,  so  that  a  so-called  solution  results. 
On  the  other  hand  they  swell  up  but  slightly  in  alcohol,  and 
are  unaffected  by  ether  and  benzol. 

In  the  same  way  proteins  all  take  up  water,  and  in  many 
cases  form  a  so-called  solution,  but  are  unaffected  by  ether 
and  benzol — a  behaviour  which  is  repeated  in  the  case  of  the 
amino-acids,  out  of  which  the  proteins  are  built  up,  and  which 
are  easily  soluble  in  water,  but  are  practically  insoluble  in 
ether  and  benzol.  On  the  other  hand,  indiarubber  and  the 
various  resins  take  up  ether,  benzol  and  turpentine  often  to  an 
indefinite  extent,  while  they  are  untouched  by  water.  With 
this  behaviour  we  may  compare  the  easy  solubility  of  the 
hydrocarbons,  the  aromatic  acids  and  esters  in  ether  and 
benzol,  and  their  insolubility  in  water.  As  Overton  has 
pointed  out,  the  power  of  amorphous  carbohydrates  to  take 
up  fluids  is  modified  by  alteration  of  their  chemical  structure 
in  the  same  direction  as  the  solubility  of  the  corresponding 
crystalline  carbohydrates.  Thus,  if  the  hydroxyl  groups  in 
the  sugars  be  replaced  by  nitro,  acetyl  or  benzoyl  groups,  they 
become  less  soluble  in  water,  while  their  solubility  in  alcohol, 
acetone,  etc.,  is  increased.  In  the  same  way  the  replacement 
of  the  hydroxyl  groups  in  cellulose  by  NO2  groups  diminishes 
the  power  possessed  by  this  substance  of  taking  up  water,  but 


PHYSICAL  PROPERTIES  OF  PROTOPLASM  17 

renders  it  capable  of  swelling  up  or  dissolving  in  alcohol  and 
acetone. 

Instahility  of  Colloidal  Solutions. — It  is  probably  to  the 
relatively  large  size  of  the  molecules  or  particles  of  which 
they  are  composed,  that  we  must  refer  the  unstable 
character  of  most  colloidal  solutions.  The  colloid  can  be 
precipitated  in  association  with  a  certain  amount  of  the 
solvent,  or  the  whole  mass  can  be  turned  into  a  gel  by  very 
various  means,  such  as  the  addition  of  electrolytes,  by  heating 
or  mechanical  agitation,  or  by  the  addition  of  some  other 
colloid.  In  this  precipitation  an  important  part  is  played 
by  the  fact  that  colloidal  particles,  like  the  ions  in  a  solution 
of  sodium  chloride,  in  many  cases  carry  electric  charges.  The 
mutual  repulsion  of  the  j)articles  thus  brought  about  helps  to 
keep  them  in  suspension.  If  they  are  robbed  of  their  charge 
by  addition  of  an  electrolyte,  by  the  passage  of  a  current,  or 
by  the  addition  of  an  oppositely  charged  colloid,  this  mutual 
repulsion  is  done  away  with,  the  particles  aggregate  and  fall 
to  the  bottom  as  a  precipitate.  It  must  be  remembered  that, 
even  when  precipitation  has  been  brought  about  by  one  of 
these  means,  the  association  between  the  colloid  and  water 
has  not  been  destroyed,  but  the  precipitate  still  contains  a 
large  amount  of  imbibed  water,  which  can  be  removed  only 
by  the  application  of  a  considerable  force.  The  essence  of 
the  change  which  has  taken  place  consists  in  the  conversion 
of  a  colloid  with  unlimited  powers  of  swelling  in  water  into  a 
colloid  whose  powers  of  imbibition  are  limited,  as  is  the  case 
with  an  animal  material  such  as  white  fibrous  tissue. 

Surface  Phenomena  of  Colloidal  Particles. — The  great  size  of 
the  molecules  or  molecular  aggregates,  which  are  present  in 
colloidal  solutions,  justifies  us  in  ascribing  to  them  definite 
surfaces  and  therefore  properties  which  are  associated  with 
any  surface.     The  distribution  of  a  substance  within  a  fluid 

F.B.  c 


18  THE    FLUIDS    OF    THE    BODY 

as  a  rule  is  not  the  same  as  its  distribution  on  the  free 
surface  of  the  fluid.  Thus,  if  a  dissolved  substance  diminishes 
the  surface  tension  of  the  fluid  it  will  tend  to  accumulate 
at  the  surface  in  greater  concentration  than  in  the  interior 
of  the  fluid.  Moreover,  in  contact  with  a  surface,  the  pressure 
either  of  gases  or  of  vapours  tends  to  be  diminished,  and 
it  is  probable  that  the  same  rule  applies  to  many  dissolved 
substances.  Thus  it  is  impossible  to  get  rid  of  the  last  traces 
of  air  from  a  vessel  by  one  evacuation.  The  air  adheres  with 
such  tenacity  to  the  superficial  layer  of  the  glass  that  repeated 
heating  and  evacuation  are  necessary  in  order  to  remove  the 
last  traces.  This  power  possessed  by  surfaces  of  diminishing 
gas  or  vapour  tension,  and  therefore  of  condensing  substances 
on  themselves,  is  spoken  of  as  adsorption.  In  a  sol  the 
surface  of  the  particles  must  be  enormous  in  proportion  to 
their  total  mass.  This  will  be  evident  if  we  consider  the 
effects  of  minute  subdivision  in  increasing  surface.  A  sphere 
of  10  ccm.  would  have  a  surface  of  22  sq.  cm.  If  the  sphere 
were  reduced  to  a  fine  powder,  consisting  of  spherules,  each 
of  which  was  0*00000025  cm.  in  diameter,  the  total  surface 
of  the  solid  would  amount  to  20,000,000  sq.  cm.,  i.e.,  nearly 
half  an  acre.  At  the  whole  of  this  surface  adsorption  may 
take  place,  involving  the  concentration  of  electrolytes  or  gases. 
The  behaviour  of  each  particle  will  thus  be  determined,  not 
only  by  its  own  nature,  but  also  by  that  of  the  little  court 
of  adsorbed  material  by  which  it  is  surrounded.  So  great  is 
this  power  of  adsorption  that  it  is  practically  impossible  to 
get  rid  of  the  last  traces  of  ash,  i.e.,  adsorbed  electrolyte, 
from  a  gel  by  physical  means,  such  as  washing  with  distilled 
water. 

This  power  of  adsorption  is  not  however  indiscriminate. 
It  is  determined,  not  only  by  the  extent  of  surface  afforded  by 
the  particles,  but  also  by  the  chemical  nature  of  the  particles 


PHYSICAL  PROPERTIES  OF  PROTOPLASM  19 

themselves.  This  is  shown  by  the  varying  affinity  for  dye- 
stuffs  of  substances  of  different  chemical  composition,  and 
may  be  illustrated  by  the  behaviour  of  the  colloids  which  play 
an  important  part  in  the  building-up  of  the  animal  cell. 
Thus,  as  Hardy  has  pointed  out,  the  globulin  of  blood  serum 
may  occur  in  four  different  states,  viz.,  globulin  itself,  com- 
pounds of  globulin  with  acid  or  with  alkali,  and  compounds 
of  globulin  with  neutral  salts.  The  amount  of  acid  or  alkali 
combining  with  the  globulin  is  indeterminate,  the  effect  of 
adding  either  acid  or  alkali  to  the  neutral  globulin  being  to 
cause  a  gradual  conversion  of  an  opaque  milky  suspension 
into  a  limpid,  transparent  solution.  On  drying  HCl  globulin 
the  dried  solid  is  found  to  contain  all  the  chlorine  of  the  HCl 
used  to  dissolve  it.  The  acid  must  therefore  be  regarded 
as  being  in  true  combination.  Both  acid  and  alkali  globulins 
act  as  electrolytes,  and  the  globulin,  being  electrically  charged, 
takes  part  in  the  transport  of  electricity.  In  order  to  produce 
the  same  extent  of  solution,  the  concentration  of  alkali  added 
must  be  double  that  of  the  acid.  The  relation  of  globulin 
to  acids  and  alkalies  is  similar  to  that  of  the  so-called  ampho- 
teric substances,  such  as  the  amino-acids.  An  amino-acid 
such  as  glycin  can  react  as  a  basic  anhydride  with  other  acids, 
thus : — 

/■^^'  /NH2  -  HCl 

CH2  +  HCl  =  CH2< 

\C0-0H  ^COOH 

or  as  an  acid  anhydride  with  bases.  Like  these  too,  globulin 
forms  soluble  compounds  with  neutral  salts. 

From  true  electrolytes,  colloidal  solutions  differ  in  the  fact 
that  their  particles  are  of  varying  size  according  to  the 
condition  in  which  they  exist,  and  carry  varying  charges  of 
electricity,  whereas  an  ion,  such  as  Na'  or  CI',  has  a  mass 
which  is  constant  for  the  ion  in  question,  and  always  carries 

c  2 


20  THE    FLUIDS    OF    THE    BODY 

the  same  electric  charge.     The  charged  particles  of  an  acid  or 
alkali-globulin  may  be  distinguished  therefore  as  pseud-ions. 

In  these  adsorption  combinations,  although  the  chemical 
nature  of  the  colloidal  molecules  is  concerned,  there  is  an 
absence  of  definite  equilibrium  points,  such  as  we  are  accus- 
tomed to  find  in  most  chemical  reactions.  The  inertia  of  the 
system  and  the  large  size  of  the  molecules  determine  the 
occurrence  of  false  equilibria  and  of  delayed  reaction.  Thus 
the  condition  and  behaviour  of  a  colloidal  system  at  any 
moment  are  determined,  not  entirely  by  the  quantitative 
relations  of  its  components,  but  also  by  the  past  history  of  the 
system.  On  account  of  this  inertia,  any  change  in  a  colloidal 
system  will  tend  to  become  indefinitely  slow,  i.e.,  practically 
to  cease,  before  complete  equilibrium  is  attained.  Any  system 
of  this  nature,  with  which  we  may  have  to  deal,  may 
be  regarded  as  in  a  condition  of  stress,  the  direction  of 
the  stress  being  determined  by  that  of  the  transformation  to 
which  the  system  was  last  subjected.  Such  a  system  has 
what  we  might  loosely  speak  of  as  memory — a  memory  which 
would  favour  the  continuance  of  an  antecedent  process,  and 
oppose  the  occurrence  of  a  process  in  the  reverse  direction. 
In  order  to  destroy  a  configuration  that  is  once  established  we 
have,  in  consequence  of  the  inertia  *of  the  system,  to  overstep 
widely  the  conditions  of  its  formation.  Thus  a  10  per  cent, 
solution  of  gelatin  sets  at  21°  C.  but  does  not  melt  until 
warmed  to  29*6°  C.  Solutions  of  agar  in  water  set  at  about 
35*^  C.  but  do  not  melt  under  90°  C.  A  gel  of  gelatin  takes 
twenty-four  hours  after  setting  before  it  attains  a  constant 
melting  point. 

Surface  Phenomena  of  Colloidal.  Solutions  {Sols). — A  gel 
differs  from  an  ordinary  solid  in  that  it  is  freely  permeable 
by  water  and  by  most  dissolved  crystalloids.  Sodium  chloride 
diffuses    with   practically  the    same    rapidity  through   a   gel 


PHYSICAL  PROPERTIES  OF  PROTOPLASM  21 

composed  of  5  per  cent,  gelatin  as  through  pure  water.  So 
far  as  concerns,  however,  the  particles  or  molecules  of  the 
colloid  responsible  for  the  formation  of  the  gel,  this  resembles 
an  ordinary  solid  in  that  the  molecules  are  constrained  to 
occupy  a  particular  position  and  are  not  free  to  move  within 
the  gel. 

In  a  sol,  on  the  other  hand,  the  colloidal  particles  are  freely 
moveable  among  themselves,  though,  in  consequence  of  their 
great  size  and  inertia,  any  movement  determined  by  differences 
in  concentration  will  occur  at  an  infinitely  slower  rate  than 
is  the  case  with  smaller  molecules,  such  as  NaCl. 

I  have  already  mentioned  that  any  fluid  at  its  surface 
possesses  different  qualities  to  those  possessed  by  it  in  its 
interior,  and  that,  for  instance,  any  dissolved  substance 
which  diminishes  the  surface  tension  of  the  solvent  tends  to 
accumulate  in  greater  concentration  at  the  surface.  Almost 
all  colloids  with  which  we  are  acquainted  possess  this  property 
of  diminishing  surface  tension,  and  on  this  account  tend  to 
accumulate  in  greater  concentration  at  the  surface.  Owing  to 
the  enormous  size  of  the  colloidal  molecules,  a  considerable 
increase  of  concentration  is  not  possible  without  bringing  the 
particles  within  each  other's  sphere  of  influence,  so  that  they 
may  be  regarded  as  actually  touching.  We  thus  get  formed 
at  the  surface  of  the  hydrosol— such  as  one  of  albumen — 
an  actual  solid  pellicle  or  gel  composed  of  egg-albumen. 
Every  fluid  mass  of  colloid  in  the  body  will  tend  at  its  surface 
to  become  coated  with  such  a  gel  or  pellicle,  which  will  resist 
deformation  and  extension  and  the  properties  of  which  will 
determine  the  access  of  fluids  or  solids  to  the  hydro-sol 
within. 

Although  we  have  spoken  of  protoplasm  as  essentially  fluid 
and  composed  of  different  hydrosols  of  varying  complexity, 
it  is  evident  that  each  mass  of  protoplasm  will  present  solid 


22  THE    FLUIDS    OF    THE    BODY 

or  gel  pellicles  at  its  periphery,  as  well  as  at  any  part  in  its 
interior  where  chemical  differences  determine  the  production 
of  a  surface  with  a  definite  surface  tension.  By  the  greater 
or  less  formation  of  such  pellicles  we  may  explain  the  varying 
rigidity  of  different  forms  of  living  tissue  and  the  varying 
accessibility  or  permeability  of  different  cells  to  the  entrance 
or  passage  of  the  different  constituents  of  their  surrounding 
medium. 

In  this  way  chemical,  physical,  and  structural  organisation 
will  go  hand  in  hand.  Every  cell  may  be  looked  upon  as 
formed  of  one  or  more  molecules  of  extreme  complexity  in 
which  proteins,  fats,  phosphorised  fats,  and  carbohydrates  are 
bound  together  in  one  immense  complex,  so  large,  in  fact, 
that  it  may  present  different  chemical  reactions  according  to 
the  situation  at  which  any  reaction  is  excited.  The  varying 
chemical  structure  at  different  parts  of  this  molecule  will 
determine  a  behaviour  of  the  whole  molecule,  or  molecules, 
constituting  the  cell,  which  will  be  conditioned  by  spatial 
relationships.  In  consequence  of  the  heterogeneous  character 
of  the  molecule,  substances  will  be  produced  in  different  parts 
of  the  cell  which  are  immiscible  with  the  surrounding  fluid, 
and  will  therefore  become  separated  off  by  colloidal  pellicles ; 
and  the  nature  of  these  films  will  determine  the  subsequent 
relations  between  the  secretory  vacuole  and  the  surrounding 
protoplasm. 

A  study  of  the  chemistry  of  the  cell  enables  us  therefore  to 
form  a  conception  of  the  manner  in  which  its  varying 
behaviour,  according  to  the  nature  of  the  environment,  is 
brought  about ;  since  the  relation  of  the  cell  to  its  environ- 
ment, as  well  as  the  inter-relation  of  its  parts  among  them- 
selves, must  depend  on  the  qualities  of  the  pellicles  bounding 
the  surfaces  of  separation. 

It  may  be  interesting  at  this  point  to  consider  shortly  the 


PHYSICAL    PROPERTIES    OF    PROTOPLASM  23 

main  features  which  determine  the  qualities  of  such  a  mem- 
brane and  the  transference  across  it  of  various  substances  in 
sokition.  In  my  next  lecture  I  shall  have  to  deal  with  the 
effects  of  this  bounding  membrane,  or  '  Plasmahaut,'  on  the 
interchanges  between  the  cell  and  the  surrounding  medium, 
as  determined  by  experiments  on  living  cells.  In  our  physical 
experiments  it  is  not  easy  to  reproduce  such  a  membrane  of 
molecular  dimensions.  There  is  no  reason,  however,  to  believe 
that  the  results  of  experiment  on  thicker  membranes  differ 
essentially  in  any  other  respects  than  in  time-relations  from 
the  phenomena  which  would  be  presented  if  their  thickness 
were  reduced  to  that  of  a  single  molecule.  The  transference 
across  any  colloidal  membrane  depends  on  its  permeability, 
that  is  to  say,  on  the  substances  which  it  will  allow  to  pass. 
The  permeability  of  such  membranes  to  any  given  substance 
is  apparently  conditioned  by  the  solubility  of  the  substances 
in  the  membrane,  or  of  the  membrane  in  the  substance. 
Under  the  term  solubility  we  may  include  also  the  property  of 
imbibition,  or  '  Quellung.'  As  we  have  already  seen,  these 
qualities  are  determined  in  their  turn  by  the  chemical  nature 
of  the  substances  in  question.  The  carbohydrates,  for 
instance,  are  either  soluble  in  or  imbibe  water ;  the  resins 
and  allied  substances,  such  as  india-rubber,  vulcanite,  etc., 
will  take  up  ether  and  sometimes  alcohol,  but  are  practically 
unaffected  in  the  presence  of  water,  just  as  the  hydrocarbons 
are  soluble  in  ether  but  insoluble  in  water. 

The  same  contrast  is  seen  when  we  compare  the  permeability 
of  these  substances.  A  colloidal  membrane  composed  of  pro- 
tein or  gelatin,  or  allied  substances,  is  easily  permeable  by 
water  as  well  as  by  substances  dissolved  in  water,  such  as  salt 
and  sugar.  It  is  less  permeable  to  ether  and  practically 
impermeable  to  substances  such  as  benzol  or  hydrocarbons, 
or  fats.     On  the  other  hand,  a  disc  of  india-rubber  or  vulcanite 


24  THE    FLUIDS    OF    THE    BODY 

allows  no  water  to  pass,  but  is  easily  permeable  to  ether  or 
benzol.  Thus  if  two  closed  vessels,  containing  ether  and  alcohol 
respectively  and  connected  with  manometers,  be  separated 
by  a  disc,  the  passage  of  fluid  will  depend  on  the  nature  of 
the  disc.  If  the  disc  be  of  vulcanite,  ether  passes  into  the 
alcohol  and  causes  a  great  development  of  osmotic  pressure  on 
the  alcohol  side.  If  however  the  disc  be  of  moist  animal 
membrane — such  as  pig's  bladder — the  passage  is  in  the 
opposite  direction,  viz.,  of  alcohol  into  ether,  and  the  develop- 
ment of  pressure  is  on  the  side  of  the  ether.  We  shall  later 
have  occasion  to  illustrate  this  dependence  of  permeability  on 
chemical  relationships  between  the  membrane  and  the  dissolved 
substances. 

Another  important  quality  of  these  surface  pellicles,  which 
will  play  the  greater  part  the  more  microscopic  the  dimensions 
involved,  is  their  surface  tension.  The  effect  of  surface  tension 
may  be  regarded  as  equivalent  to  a  contracting  force,  the 
surface  continually  striving  to  attain  its  smallest  possible  area, 
just  as  an  inflated  india-rubber  ball  tends  to  collapse  in  conse- 
quence of  the  tension  of  the  rubber  membrane.  With 
ordinary  drops  or  masses  of  fluid,  the  effect  of  this  surface 
tension  on  the  pressure  in.  the  interior  of  the  fluid  is  practically 
negligible.  The  actual  pressure  exerted  will  however  vary 
inversely  as  the  dimensions  of  the  mass.  Thus  in  a  sphere 
where  P  is  the  pressure,  A  is  a  constant  depending  on  the 
nature  of  the  fluids  in  contact,  and  R  is  the  radius  of  the 
sphere,  the  pressure  would  be  given  by  the  following  equation : 

2A 

P  =  ^ .      The  smaller  the  drop  therefore,  the  greater   the 

pressure.  In  very  minute  drops  the  pressure  might  well 
amount  to  several  atmospheres. 

This  pressure  might  be  of  considerable  importance  in  deter- 
mining  the   relations   between   the  contents  of   the   minute 


PHYSICAL    PROPERTIES    OF    PROTOPLASM  25 

vacuoles,  which  occur  to  such  a  large  extent  in  secreting 
cells,  and  the  surrounding  protoplasm.  If  a  substance  were 
present  both  within  and  without  the  vacuole,  to  which  the 
pellicle  bounding  the  vacuole  was  impermeable,  it  is 
evident  that  a  great  hydrostatic  pressure  within  the  vacuole 
determined  by  the  surface  tension  might  give  rise  to  important 
differences  of  concentration  within  and  without  the  vacuole. 
It  is  possible  that  this  factor  might  play  a  part  in  determining 
the  marked  differences  of  concentration  which  are  found  to 
exist  between  the  blood  and  the  product  of  secretion  of  many 
glands,  differences  which  involve  work  on  the  part  of  the  cells, 
and  therefore  the  existence  of  a  '  machine '  with  the  mechanism 
of  which  we  are  at  present  entirely  unacquainted. 

Surface  tension  must  also  determine  the  form  of  any  cell  or 
any  part  of  a  cell.  The  surface  tension  between  a  cell  and  its 
surrounding  medium,  e.g.,  water,  depends,  as  we  know, 
entirely  on  the  chemical  nature  of  the  surface.  Alter  this 
surface  in  the  slightest  degree,  as,  e.g.,  by  the  deposition  of  a 
few  ions  of  one  charge  or  another,  and  we  at  once  alter  the 
surface  tension  between  the  cell  and  its  surroundings,  and 
with  this  also  the  electrical  conditions  of  the  surface. 

In  recent  times  MacDonald  has  shown  how  such  minute 
changes  of  concentration  at  the  surface  of  the  nerve  fibrils 
may  possibly  account  for  the  projDagation  of  a  nerve  impulse 
as  a  result  of  local  disturbances  or  excitation.  At  the  present 
time  i  want  especially  to  call  your  attention  to  the  fact  that  a 
slight  chemical  change  limited  to  part  of  a  spherical  cell  will 
alter  the  surface  tension  at  this  spot.  If  the  surface  tension  is 
increased,  the  pellicle  will  contract  and  may  cause  a  depression 
in  the  neighbouring  part  of  the  cell.  If  on  the  other  hand 
the  surface  tension  be  diminished,  the  effect  will  be  the  same 
as  the  sudden  thinning  of  a  small  part  of  the  wall  of  a  rubber 
balloon.      The  tension  of   the  rest  of   the   wall   causes   the 


26  THE    FLUIDS    OF    THE    BODY 

contents  of  the  balloon  to  bulge  out  through  the  thinner 
portion  of  the  wall.  An  analogous  change  occurring  in  the 
boundary  layer  of  an  amoeba  will  bring  about  the  protrusion 
of  a  pseudopodium.  If  we  assume  with  Bernstein  that  in  its 
ultimate  structure  a  muscle  consists  of  chains  of  oval  particles, 
whose  form  is  determined  by  the  constraining  effect  of  an 
elastic  pressure  on  a  fluid  sphere  with  a  high  surface  tension, 
it  is  evident  that  any  chemical  change,  which  will  increase  this 
tension,  will  cause  the  particles  to  approach  more  nearly  to  a 
spherical  form,  and  thus  bring  about  a  thickening  and  shorten- 
ing of  the  whole  muscle.  The  energy  of  a  muscular  contrac- 
tion would  thus  be,  in  the  last  instance,  referable  to  the  energy 
of  surface  tension. 

I  hojDe  to  have  shown  you  in  this  lecture  that  our  knowledge 
of  the  properties  of  colloidal  solutions,  in  which  water  forms  so 
essential  a  part,  although  still  so  limited,  enables  us  neverthe- 
less to  form  a  conception  of  the  mechanism  underlying  many 
of  the  phenomena  which  we  regard  as  distinctive  of  living 
organisms. 


LECTUEE    II 

THE    OSMOTIC    EELATIONSHIPS    OF    CELLS 

In  my  last  lecture  I  drew  your  attention  to  the  marked 
difference  which  is  found  to  exist  between  the  elementary 
composition  of  living  organisms,  and  that  of  the  medium  in 
which  they  live,  and  to  the  fact  that  similar  differences  are 
found  when  we  compare  the  cells  forming  part  of  a  complex 
organism,  such  as  man,  with  the  internal  media,  such  as 
blood,  with  which  they  are  continually  in  contact. 

The  composition  of  any  cell  is  something  peculiar  to  itself. 
Kegarding  as  we  do  the  variability  in  the  reactions  of  different 
kinds  of  organisms  or  of  cells  as  conditioned  by  the  chemical 
structure  of  their  protoplasm,  it  is  only  natural  that  the 
differences  in  the  chemical  compositions  o£  different  organisms 
are  almost  as  marked  as  those  ruling  between  the  organisms 
and  their  surrounding  dead  medium.  These  reactions  involve 
the  necessity  of  each  cell  being  cut  off,  so  to  speak,  from  its 
environment.  In  maintaining  this  privacy  of  cell  life,  the 
surface  layer  of  protoplasm  must  play  an  all-important  part. 
Since  it  is  by  means  of  this  layer  that  the  organism  enters 
into  relation  with  its  environment,  it  acquires  a  prime  impor- 
tance to  the  life  of  the  cell,  and  much  labour  has  been  devoted 
to  the  experimental  investigation  of  the  properties  of  the 
superficial  layer  of  the  protoplasm,  or  Plasmahaut. 

This  layer  is  not  to  be  confounded  with  the  cell-wall. 
The  latter,  which  plays  a  great  part  in  the  building  up  of 
vegetable  tissues,  is  formed  by  a  process  of  secretion  from 
the. living  protoplasm  and  is  situated  altogether  outside   the 


28  THE    FLUIDS    OF    THE    BODY  ' 

superficial  Plasmahaut.  The  cell-wall  differs  considerably  in 
its  chemical  composition  from  the  protoplasm  out  of  which 
it  has  been  formed.  In  most  plants  it  consists  of  cellulose, 
a  substance  belonging  to  the  carbohydrate  group,  and  with 
a  composition  represented  by  some  multiple  of  the  formula 
CeHioOs.  In  other  cases  the  cell-wall  may  be  built  up  from 
calcium  carbonate  or  other  lime  salts,  from  silica  or  from 
chitin,  and  may  be  perforated  to  allow  the  passage  of  com- 
municating strands  of  protoplasm  between  adjacent  cells.  It 
is  often  freely  permeable  to  all  kinds  of  solutions,  and  does 
not  in  this  case  play  any  part  in  regulating  the  interchanges 
of  the  cell  with  its  environment. 

The  superficial  layer  of  protoplasm  represents  that  part  of 
the  living  substance  which  stands  in  immediate  relationship 
to  the  environment.  Every  change  in  the  latter  can  influence 
the  living  cell  only  through  this  layer,  by  which  also  sub- 
stances must  pass  on  their  way  into  the  cell  for  assimilation, 
or  out  of  the  cell  for  excretion.  The  retention  of  individuality 
by  the  cell  must  be  determined  by  chemical  and  physical 
differences  between  this  layer  and  the  surrounding  fluid. 
Since  it  differs  from  the  rest  of  the  protoplasm  in  the  changes 
to  which  it  is  subject,  it  must  also  differ  in  its  chemical  com- 
position, apart  altogether  from  the  factors  which,  as  we  saw 
above,  determine  molecular  differences  between  the  surface 
and  the  internal  parts  of  any  colloidal  solution.  On  this 
account  we  must  assume  the  existence  of  a  definite  boundary 
layer  even  when  under  the  highest  powers  of  the  microscope 
we  can  perceive  no  differentiation  between  this  layer  and  the 
deeper  parts. 

A  cell  which  leads  its  life  in  a  fluid  environment  must 
take  up  the  greater  part  of  its  food  material  from  this 
medium  in  the  form  of  solution,  the  passage  of  food  sub- 
stances from  the  medium  into  the   body  of   the  cell  being 


THE  OSMOTIC  RELATIONSHIPS  OF  CELLS  29 

determined  by  the  permeability  of  the  superficial  protoplasm. 
The  immiscibility  of  the  protoplasm  with  the  surrounding 
fluid  shows  that  the  permeability  of  the  membrane  must  be 
a  limited  one.  The  qualitative  permeability  can  be  easily 
studied  in  vegetable  cells.  These  present  within  a  cellulose 
wall  a  thin  layer  of  protoplasm  (the  primordial  utricle), 
enclosing  a  cell  sap.  If  the  root  hairs  of  Tradescantia  be 
immersed  in  a  10  per  cent,  solution  of  glucose  or  in  a  2  to  3 
per  cent,  solution  of  salt,  a  process  of  plasmoli/sis  takes  place. 
The  cell  sap  diminishes  in  amount  by  the  diffusion  of  water 
outwards,  so  that  the  primordial  utricle  shrinks.  On  immersing 
the  cells  in  distilled  water,  water  passes  into  the  cell  sap 
in  increasing  amount  until  the  further  expansion  of  the 
protoplasmic  layer  is  prevented  by  the  tension  of  the  surround- 
ing cell-w^alls.  This  behaviour  can  only  be  explained  on  the 
assumption  that  the  protoplasm  is  impermeable  both  to  sugar 
and  to  salt,  but  is  freely  permeable  to  molecules  of  water,  i.e., 
it  behaves  as  a  '  semi-permeable  '  membrane.  Similar  experi- 
ments can  be  made  on  animal  cells.  The  most  convenient  for 
this  purpose  are  the  red  blood  corpuscles.  These  also  shrink 
when  immersed  in  salt  solution  with  a  greater  molecular  con- 
centration than  would  correspond  to  the  plasma  of  the  blood 
from  which  the  corpuscles  are  derived  ;  whereas,  if  placed  in 
weak  salt  solution  or  distilled  water,  they  swell  up  and  burst, 
discharging  their  haemoglobin  in  solution  into  the  surround- 
ing fluid.  By  comparison  of  various  salts  it  is  found  that  the 
strength  of  each  salt  solution  which  is  just  necessary  to  cause 
plasmolysis,  or  haemolysis  as  the  case  may  be,  is  determined 
entirely  by  its  molecular  concentration,  i.e.,  a  decinormal 
solution  of  sodium  chloride  will  be  equivalent  in  its  effects  on 
the  cells  to  a  decinormal  solution  of  potassium  nitrate  or  of 
sodium  sulphate.  This  impermeability  of  the  plasma  skin 
does   not  apjDly  to  all   dissolved   substances.     Thus   Overton 


30  THE    FLUIDS    OF    THE    BODY 

has  found  that,  whereas  this  layer  is  practically  impermeable 
to  salts,  hexoses,  and  amino-acids,  it  permits  the  easy  passage  of 
monatomic  alcohols,  aldehydes,  alkaloids,  etc.  All  these 
substances  are  more  soluble  in  ether,  oil,  and  similar  media 
than  they  are  in  water.  The  passage  of  dissolved  substances 
through  a  medium  wetted  by  the  solvent  depends  on  the 
solubility  of  these  substances  in  the  membrane,  and  Overton 
therefore  concludes  that  the  superficial  layer  of  protoplasmic 
cells  must  itself  partake  of  a  '  lipoid '  character,  and 
that  cholesterin  and  lecithin  probably  enter  largely  into  its 
composition.  Thus  only  those  dyes  which  are  soluble  in  a 
mixture  of  melted  lecithin  and  cholesterin  have  the  property 
of  penetrating  the  living  cell,  and  it  is  only  these  dyes,  such  as 
methylene  blue,  neutral  red,  etc.,  which  can  be  used  for  intra 
vitam  staining.  For  the  same  reason  substances  which  have 
the  power  of  dissolving  lecithin  and  cholesterin,  such  as  ether 
or  bile  salts,  also  act  as  haemolytic  agents,  i.e.,  they  cause  a 
destruction  of  the  red  blood  cells  by  dissolving  the  superficial 
layer  which  is  necessary  for  their  preservation  from  the 
solvent  effects  of  the  surrounding  fluid. 

These  results  seem  at  first  to  land  us  in  difficulty.  Since 
the  superficial  layer  of  the  protoplasm  is  impermeable,  so  far 
as  our  experimental  results  go,  to  the  greater  number  of 
dissolved  salts,  one  might  expect  that  the  cells  would  be 
indifferent  to  the  qualitative  composition  of  the  medium  and 
would  be  affected  only  by  its  qualitative  composition,  i.e.,  by 
the  total  osmotic  pressure  of  the  surrounding  fluid.  This  is  far 
from  being  the  case. 

It  was  shown  long  ago  in  Ludwig's  laboratory  that  the 
inorganic  constituents  of  blood  serum  played  an  important 
part  in  determining  the  heart-beat,  and  Einger  taught  us  to 
discriminate  between  the  physiological  effects  of  calcium, 
potassium,  and  sodium  salts  and  to  assign  to  each  of  these 


THE  OSMOTIC  RELATIONSHIPS  OF  CELLS  31 

salts  a  specific  action  in  the  regulation  of  the  cardiac  activity. 
Whereas  we  can  inject  litres  of  sodium  chloride  solution  into 
an  animal's  vein  without  ill  effects,  a  few  cubic  centimetres  of 
solution  of  potassium  chloride  will  bring  about  death  by 
failure  of  the  heart.  The  same  sensitiveness  of  the  animal 
cell  to  qualitative  differences  in  the  composition  of  the 
surrounding  medium  is  shown  in  some  interesting  observations 
of  Loeb  *  on  the  conditions  of  survival  of  a  marine  crustacean, 
Gammarus,  found  in  the  Bay  of  San  Francisco.  Loeb 
pointed  out  that  when  Gammarus  was  transferred  from  bay- 
water  into  distilled  water,  respiratory  movements  stopped  in 
about  half-an-hour  and  the  stoppage  was  permanent  unless  the 
animal  was  replaced  in  the  sea-water  within  about  ten  minutes. 
If  the  Gammarus  were  put  into  a  solution  of  cane  sugar  in 
distilled  water  of  a  concentration  isosmotic  with  sea- water,  it 
died  as  rapidly  as  in  distilled  water,  and  the  same  thing 
happened  when  the  animals  were  placed  in  pure  NaCl 
solution  isosmotic  with  sea-water.  They  died  still  more 
rapidly  when  they  were  put  into  a  solution  containing  all  the 
salts  of  the  sea- water,  and  in  the  same  proportion,  with  the 
exception  of  sodium  chloride.  In  solutions  containing  NaCl, 
KCl  and  CaCl2  in  the  proper  proportion,  the  animals  lived  as 
long  as  48  hours,  and  if  a  little  MgCl2  were  then  added,  the 
animals  survived  as  long  as  in  the  ordinary  sea-water. 

We  see  therefore  that  not  only  must  the  medium  sur- 
rounding a  cell  organism  have  a  definite  osmotic  pressure, 
but  that  this  pressure  must  be  supplied  by  specific  salts. 

Are  we  to  conclude  from  these  facts  that  the  observations 
previously  mentioned  on  the  permeability  of  the  Plasmahaut 
were  wrong,  and  that  the  Plasmahaut  is  really  permeable  to 
all  these  salts,  but  that  the  passage  is  so  slow  that  it  is  not 

^  J.  Loeb.  "  The  Dy^amies  of  Living  Matter,"  p.  46.     1906, 


32  THE    FLUIDS    OF    THE    BODY 

detectable  by  our  grosser  means  of  analysis  ?  I  believe  such 
a  conclusion  would  not  really  be  warranted.  In  the  first  place 
it  is  important  to  remember  that  the  phenomena  which  we 
associate  with  life  are  most  of  them  reactions  to  stimuli. 
Every  stimulus  affects  in  the  first  place  the  surface  layer,  and 
we  have  seen  that  many  of  the  reactions  are  also  determined 
by  changes  in  this  layer.  Its  surface  tension  is  a  function 
of  its  composition,  and  therefore,  among  other  factors,  of 
the  salts  which  are  adsorbed  by  the  surface.  It  would  be 
quite  comprehensible  that,  even  though  the  salts  do  not 
penetrate  into  the  interior  of  the  cell,  variations  in  the 
composition  of  the  medium  would  alter  the  surface,  and 
thus  interfere  with  or  armul  the  reactions,  such  as  con- 
tractility, the  transference  of  gas,  or  the  assimilation  of  food, 
which  we  associate  with  the  possession  of  life. 

Such  an  explanation  will  not  suffice  to  explain  all  the  facts. 
Dextrose,  to  which  the  Plasmahaut  is  apparently  impermeable, 
can  yet  serve  as  a  very  efficient  food  for  the  cell,  and  must 
therefore  be  taken  up  by  the  latter.  Overton  has  shown  that, 
although  impermeable  to  sugar,  the  superficial  cell  layer  is 
easily  traversed  by  methyl  derivatives  of  the  sugars.  There  is 
no  doubt  that  the  relative  solubilities  of  the  absorbed  sub- 
stances in  the  cell  and  its  surroundings  respectively  must 
play  a  part  in  the  process  of  assimilation,  at  any  rate  by  lowly 
organised  cells,  and  still  more  in  the  intracellular  exchanges 
involved  in  the  processes  of  secretion  and  excretion.  When  a 
watery  solution  of  iodine  is  shaken  up  with  chloroform,  the 
latter  sinks  to  the  bottom,  carrying  with  it  the  greater  part  of 
the  iodine.  If  a  watery  solution  of  an  organic  acid,  such  as 
lactic,  be  shaken  with  ether,  the  latter  fluid  will  extract  the 
greater  quantity  of  the  acid.  In  no  case  will  the  extraction 
be  complete,  but  there  will  be  a  definite  ratio  between  the 
amount  dissolved  by  the  ether  and  the  amount  dissolved  by 


THE  OSMOTIC  RELATIONSHIPS  OF  CELLS  33 

the  water,  the  so-called  'coefficient  of  partage '  depending  on 
the  variable  solubilities  of  the  dissolved  substance  in  the  two 
menstrua.  In  the  same  way  a  mass  of  protoplasm  will  tend 
to  absorb  from  the  surrounding  medium  and  to  concentrate  in 
itself  all  those  substances  which  are  more  soluble  in  the 
colloidal  system  of  the  protoplasm  than  in  the  surrounding 
fluid.  This  process  of  absorption  may  be  carried  to  a  very 
large  extent  if  the  dissolved  substances  meet  in  the  cell  with 
any  products  of  protoplasmic  activity  with  which  they  may 
form  insoluble  compounds,  since  they  are  thereby  removed  from 
the  seat  of  action.  By  such  a  process  as  this  we  may  account 
for  the  accumulation  of  calcium  or  silicon  in  large  quantities 
in  connection  with  the  bodies  of  various  minute  organisms. 

It  is  possible  that  in  the  process  of  absorption  some  chemical 
change  in  the  sugar  might  take  place,  which  would  render  it 
more  soluble  in  the  surface  layer  of  the  protoplasm.  The 
sugar,  for  instance,  might  be  built  up  with  lecithin  to  form 
soDie  lipoid- soluble  compound  to  which  the  Plasmahaut  would 
be  permeable.  But  this  change  must  be  accomplished  by  the 
superficial  layer  itself.  We  arrive  thus  at  the  conclusion  that 
the  Plasmahaut,  though  behaving  like  a  dead  lipoid  membrane, 
such  as  can  be  made  by  soaking  silk  with  a  solution  of  lecithin 
and  cholesterin,  is  yet  in  reality  part  and  parcel  of  the  living 
protoplasm  of  the  cell,  taking  part  in  its  changes  and  absorbing 
any  substance  which  is  required  by  the  cell  at  the  moment,  i.e., 
for  which  combining  affinities  have  been  set  free  in  the  cell. 
The  physical  permeability  of  the  cell-skin  is  a  necessary  con- 
dition for  the  privacy  of  the  cell-metabolism  ;  but  it  does  not 
prevent  the  cell  taking  up  from  the  surrounding  medium  any 
constituent  which  is  lacking  to  restore  the  constitution  of  the 
protoplasm  to  the  normal. 

Nearly  all  animal  and  vegetable  cells  allow  the  free  passage 
of  water  through  their  surface  layer.     Hence  in  animal  cells, 

F.B.  D 


34  THE   FLUIDS   OF   THE   BODY 

the  osmotic  pressure  of  the  cell-contents  is  in  most  cases 
identical  with  that  of  the  sm-rounding  medium.  Laked 
blood,  for  instance,  in  which  the  red  blood  corpuscles  are 
broken  up  and  their  contents  freely  mixed  with  the  serum, 
has  the  same  osmotic  pressure,  as  judged  by  the  depression  of 
the  freezing  point,  as  the  serum  from  the  original  blood. 
Any  change  therefore  in  the  molecular  concentration  of  the 
surrounding  fluid  has,  as  its  first  effect,  an  increase  or 
diminution  in  the  size  of  the  cell,  which  takes  or  gives  up 
water  until  the  osmotic  pressure  of  its  contents  is  once  more 
equal  to  that  of  the  medium  in  which  it  is  immersed.  "Where 
this  equality  does  not  obtain  and  the  osmotic  pressure  of  the 
cell-contents  is  greater  than  that  of  the  surrounding  medium, 
a  rigid  cell- wall  is  necessary  in  order  to  prevent  the  swelling 
of  the  cell  and  the  equalisation  of  its  pressure  to  that  of  its 
surroundings.  This  is  the  case  with  nearly  all  vegetable  cells. 
In  these,  when  growing,  the  cell-contents  have  a  molecular 
concentration  equal  to  that  of  a  solution  of  1  to  1'5  per  cent. 
KNO3,  i.e.,  a  concentration  not  far  removed  from  that  of  most 
animal  cells  and  fluids. 

The  result  of  this  concentration,  which  is  found  both  in  land 
and  water  plants,  is  that  the  cell-contents  exert  a  considerable 
pressure  on  the  superficial  layer  of  protoplasm  and  through 
this  on  the  cell-wall.  The  whole  plant  is  thus  in  a  condition  of 
turgor — a  condition  which  not  only  maintains  the  rigidity  of 
the  structure,  but  is  necessary  if  the  process  of  growth  by 
intussusception  is  to  take  place.  This  uniform,  moderate 
osmotic  pressure  applies  only  to  the  actively  growing  parts  of 
the  plants.  In  cells  which  are  the  seat  of  deposition  of  soluble 
store-materials,  such  as  sugar  (I  may  instance  the  cells  of  the 
beetroot),  the  pressure  may  be  many  times  this  amount,  and  in 
certain  moulds  grown  on  concentrated  sugar  solutions  the 
osmotic  pressure  may  be  as  high  as  150  atmospheres. 


THE  OSMOTIC  RELATIONSHIPS  OF  CELLS  35 

In  plant  cells,  with  their  firm  cellulose  walls,  small  changes 
in  the  molecular  concentration  of  the  surrounding  medium 
need  not  cause  any  ill  effects,  apart  from  temporary  modifi- 
cations in  the  condition  of  turgor.  Animal  cells,  on  the 
other  hand,  must  be  extremely  susceptible  to  any  such 
changes.  The  varying  concentration  of  the  medium  in  which 
they  are  immersed  must  bring  about  a  continual  and  corre- 
sponding variation  in  size  and  content  in  water  of  the 
cell.  Moreover,  their  protoplasm  is  directly  exposed  to  the 
influence  of  the  slight  qualitative  changes  in  the  environment 
which,  as  we  have  seen,  exert  such  wide- reaching  influences 
on  all  the  cell  functions. 

A  great  stejD  in  evolution  was  taken  therefore,  when  the 
organism  secured  for  the  majority  of  its  cells  a  medium  of 
uniform  composition,  by  the  formation  of  a  body-cavity  or 
coelom,  and  the  enclosing  in  this  cavity  of  a  fluid  not  differing 
w^idely  at  first  from  the  surrounding  sea-water.  This  step 
was  typical  of  the  whole  course  of  the  evolution  which  results 
in  rise  of  type.  Even  at  the  present  time  the  position 
of  a  man  among  his  fellows,  or  of  a  man  among  other  animals, 
is  indicated  by  the  extent  to  which  he  is  able  to  create  his 
environment  and  to  keep  it  adapted  to  his  special  needs,  so 
that  he  may  never  experience  directly  the  numerous  adverse 
influences  which  are  present  just  outside  his  own  self -created 
circle.  Every  slight  deviation  of  an  ocean  current,  every 
spell  of  cold  weather,  brings  about  the  sacrifice  of  myriads 
of  living  beings,  which  are  unable  to  withstand  the  trifling 
changes  of  saline  concentration  or  temperature  thereby  in- 
duced in  their  surroundings.  The  evolution  of  a  coelom  was 
followed  by  the  appearance  of  circulatory  and  other  organs 
designed  to  maintain  the  composition  of  the  internal  medium 
constant  at  all  parts  of  the  organism  under  varying  internal 
conditions.     In   the   highest  vertebrata,    the   evolution   of   a 

D  2 


36  THE    FLUIDS    OF    THE    BODY 

thermotaxic  mechanism  has  provided  for  the  maintenance  of 
a  constant  temperature  in  this  medimn,  whatever  may  be 
that  of  the  smToundings,  and  in  ourselves  practically 
all  the  day's  energies  are  devoted  to  the  fashioning  of  an 
environment  independent  of  climatic  influences,  and  fitted 
in  every  way  to  maintain  our  functional  caj)acities  at  their 
highest  possible  level:  in  other  words,  to  make  life  worth 
living. 

I  have  stated  above  that  the  internal  medium  of  higher 
animals,  the  coelomic  fluid,  representing  blood,  lymph,  and 
tissue  fluid  in  ourselves,  was  probably  at  its  first  appearance 
simply  an  enclosed  portion  of  the  surrounding  medium  or 
sea-water.  Apart  from  the  morphological  evidence  in  favour 
of  this  statement,  we  have  striking  confirmation  in  the  saline 
constitution  of  the  lymph  and  blood-plasma  of  the  highest 
animals.  The  three  elements,  sodium,  potassium,  and 
calcium,  are  in  proportions  very  much  like  those  which  now 
obtain  in  sea-water.  The  main  differences  between  the  saline 
constituents  of  our  blood-plasma  and  those  of  sea-water  are 
(1)  the  greater  total  concentration  of  sea- water;  (2)  the 
greater  proportion  of  magnesium  in  the  latter. 

In  an  interesting  essay  published  by  Macallum  *  in  1904, 
the  reasons  for  these  analogies  and  differences  between  blood- 
plasma  and  sea-water  are  set  out  and  discussed..  He  comes 
to  the  conclusion  that  the  present  composition  of  our  blood- 
plasma  is  probably  identical  with  that  of  the  sea-water  just 
before  the  Cambrian  period,  when  animals  possessing  a  coelom 
first  made  their  appearance,  and  that  it  has  been  transmitted 
by  heredity  through  the  countless  ages  that  have  elapsed  since 
that  far-off  period.   At  that  time  the  sea-water  must  have  been 


*  ' '  The   Palaeochemistiy   of  the   Ocean   in   Eelation  to   Animal   and 
Vegetable  Protoplasm."     Trans,  oftlie  Canadian  Institute,  1903-04. 


THE  OSMOTIC  RELATIONSHIPS  OF  CELLS  87 

much  less  concentrated  than  it  is  at  present,  since  the  con- 
stant carrying  of  the  sahne  constituents  of  the  soil  by  the 
rivers  to  the  sea,  and  the  removal  of  water  from  the  latter 
by  evaporation,  must  tend  to  cause  a  steady  increase  in  the 
saline  concentration  of  the  ocean  water. 

In  this  essay  Macallum  also  attempts  to  account  for  the 
marked  difference  between  the  constitution  of  animal  cells 
and  that  of  their  surrounding  internal  medium.  The 
beginnings  of  life  must  be  placed  far  back  in  the  pre- 
Cambrian  period.  Millions  of  years  may  have  elapsed  before 
the  evolving  protoplasm  or  protoplasms  attained  the  com-, 
plexity  of  type  which  is  now  common  to  every  cell  whether 
animal  or  vegetable.  The  universality  of  this  type  shows 
that  both  animal  and  vegetable  cells  must  be  derived  from  a 
single  type  which  existed  in  the  first  dawnings  of  life  on  the 
globe  and  which  pushed  aside  all  the  other  infinite  varieties 
of  reacting  protoplasm  which  may,  and.  indeed  must,  have 
come  into  existence  at  one  time  or  other  during  the  history 
of  this  globe.  In  this  single-celled  organism  was  elaborated 
the  whole  process  of  nuclear  division  with  its  peculiar  morpho- 
logical features,  which  have  continued  almost  unchanged 
through-  an  infinity  of  generations  animal  and  vegetable. 
"  If  now,"  Macallum  asks,  "  heredity  is  so  powerful  in  regard 
to  structure,  is  it  a  negligible  force  in  regard  to  chemical 
composition  ?  "  In  answer  to  this  query,  he  suggests  that 
the  proportions  of  saline  constituents  found  in  protoplasm 
may  conceivably  represent  those  of  •  the  salts  in  the  primeval 
ocean  in  which  life  probably  first  made  its  appearance. 

The  proportions  of  potassium,  calcium,  sodium,  and  mag- 
nesium in  living  protoplasm  are  not  yet  known,  since 
protoplasm  has  the  power  of  precipitating  these  salts  as  inert 
compounds  in  itself  or  in  its  cell- wall.  It  is  certain  however 
that  the  proportions  both  of  potassium  and  calcium  to  sodium 


38  THE    FLUIDS    OF    THE    BODY 

in  living  protoplasm  are  much  higher  than  is  the  case  either 
in  sea-water  or  in  the  coelomic  fluid,  or  in  the  lymph  or 
blood  of  higher  animals.  When  we  examine  the  composition 
of  the  lakes  and  rivers  which  derive  their  water  from  areas  in 
which  pre-Cambrian  formations  predominate,  we  find  a  corre- 
sponding excess  of  calcium  and  potassium  over  sodium,  as 
compared  with  sea-water.  Thus  in  the  lakes  of  the  Bavarian 
highlands  the  amount  of  potassium  is  twice  that  of  the 
sodium.  The  calcium  is  in  nearly  all  cases  very  abundant, 
and  in  fact  forms  the  chief  saline  constituent  of  the  water. 

At  the  first  formation  of  an  ocean  basin,  which  occurred  in 
consequence  of  the  gradual  cooling  of  the  earth's  surface,  and 
the  condensation  of  the  water  previously  present  in  the 
atmosj)here  in  the  form  of  vapour,  the  condensing  water 
would  decompose  the  hot  rocky  crust  and  wash  out  the  soluble 
products  of  decomposition.  The  condensation  of  superheated 
water  would  convert  tbe  chlorides  of  magnesium,  iron,  and 
aluminium  into  magnesia,  ferric  oxide  and  alumina,  all  of 
which  are  practically  insoluble ;  while  the  other  chlorides, 
viz.,  sodium,  potassium  and  calcium,  would  be  dissolved  out 
of  the  rock  in  amounts  depending  on  their  relative  solubility. 
The  chief  saline  constituent  of  the  water  flowing  into  the 
ocean  basin  would  be  these  chlorides,  calcium  chloride  being 
largest  in  amount,  while  potassium  chloride  would  be  more 
abundant  than  the  corresponding  sodium  compound. 

If  protoplasm  was  formed  at  this  time  from  some  poly- 
merising organic  compound  in  the  sea-water,  it  is  readily  to 
be  comprehended  that  it  should  contain  saline  constituents 
corresponding  in  proportion  and  amount  to  those  of  the  sur- 
rounding sea-water.  The  fundamental  condition  of  all  life 
and  of  the  formation  of  living  from  dead  material  is  segrega- 
tion and  reproduction  by  division,  so  that  the  proportion  of 
salts,    once  established  in  a  successful  type,  would  tend  to 


THE  OSMOTIC  RELATIONSHIPS  OF  CELLS  39 

continue  with  but  slight  modifications  through  the  millions  of 
years  which  have  since  elapsed.     The  saline  constituents  of 
protoplasm    would   therefore  not  partake  of  the   continuous 
change  whicli  has  since  been  effected  in  the  composition  of 
sea-water.     In  the  latter  the  continual  access  of  carbonates, 
and  later  the   active  intervention  of  living  organisms,  have 
tended  to  remove  a  large  amount  of  the  calcium  and  cast  it  to 
the  bottom  of  the  sea  to  form  the  masses  of  limestone  and 
chalk,  which  are  now  so  conspicuous  an  element  in  the  earth's 
crust.     In  the  same  w'ay  the  potassium  fixed  first  by  the  living 
elements   has   been  throw^n  down   in   combination   with  the 
silicates  of  alumina  in  the  form  of  clay,   so  that  finally  the 
present  composition  of  the  sea  has  been  arrived  at,  in  which 
sodium  chloride  predominates  over  all  the  other  constituents. 
Whatever  the  origin  of  the  c^lomic  fluid,  it  represents  now 
in  higher  animals  the  internal  medium  for  all  the  cells  of  the 
body.     In  order  that  these  may  be  shielded  from  the  stress  of 
circumstances  and  enabled  to  devote  their  whole  energies  to  the 
special  function  for  which  they  have  been  differentiated,  the 
organism  must  be  provided  with  distinct  mechanisms  for  the 
regulation  of  the  amount,  the  composition,  and  the  molecular 
concentration  of  this  fluid.    This  office  is  subserved  by  a  variety 
of  organs.    Excess  of  water  or  salts  or  effete  material,  the  pro- 
ducts of  the  activity  of  the  cells,  are  eliminated  largely  by  the 
agency  of  the  kidneys.    In  many  animals  there  is  also  loss  from 
the  surface  of  the  body  and  from  the  internal  surface  of  the 
lungs.    This  loss  both  of  water  and  salts  has  to  be  made  up  by 
the  agency  of  the  alimentary  canal,  i.e.,  from  without.      In 
the  higher  animals  the  coelomic  fluid  is  divided  into  several 
categories,    that    circulating   within   the    blood-vessels,    that 
subject  to    a    slow  current    in  the   lymphatic   channels,   and 
the   more  or    less    stationary    fluid  which    bathes  every  cell 
of  the  body.     It  is  this  last,  vi^.,   the  tissue  fluid,  which  ig 


40  THE    FLUIDS    OF    THE    BODY 

the   most   important   for   the  vital   activity  of   the   body   as 
a  whole. 

I  propose  in  the  following  lectures  to  describe  some  of  the 
mechanisms  by  which  the  composition  and  amount  of  this 
internal  medium  of  the  body  are  regulated,  and  to  discuss  the 
physical  forces,  intra-  and  extra-  cellular,  involved  in  their 
work. 


LECTUEE   III 


THE    INTAKE    OF    FLUID 


In  all  the  higher  animals  the  cells,  of  which  their  bodies  are 
composed,  are  bathed  by  an  internal  medium,  from  which  the 
cells  derive  their  nourishment,  and  into  which  they  discharge 
their  waste  products.  By  the  provision  of  such  an  internal 
medium,  the  cells  obtain  an  average  constancy  of  environ- 
ment and  are  withdrawn  from  the  buffeting  and  constant 
changes  to  which  the  animal  as  a  W'hole  is  exposed.  They 
are  thus  enabled  to  devote  their  entire  energies  to  the  dis- 
charge of  their  particular  functions  in  the  commonwealth  of 
the  body.  By  this  means  moreover  provision  is  made  for 
maintaining  the  solidarity  of  the  component  parts  of  the 
commonwealth.  The  products  of  any  one  set  of  cells  are 
able  to  influence  the  activity  of  the  cells  in  remote  parts 
of  the  body,  and  in  some  cases  it  has  been  shown  that  special 
chemical  messengers  are  poured  out  into  the  tissue  fluids  for 
the  express  purpose  of  effecting  this  chemical  integration  and 
of  bringing  about,  in  widely  diverse  tissues,  the  united  action 
to  a  common  end  which  is  characteristic  of  all  the  higher 
types  of  living  organisms. 

Constancy  of  medium  is  not  secured  however  simply  by  the 
enclosure  of  a  certain  amount  of  sea-water  in  the  body  cavity. 
Every  cell  is  continuously  engaged  in  taking  up  food  sub- 
stances from  the  internal  medium  and  in  discharging  waste 
products  into  it.  In  order  that  the  organism  may  maintain  a 
certain  average  composition  of  its  body  fluids  and  thus  really 
create  the   environment  of  its  constituent  cells,   it  must  be 


42  THE    FLUIDS    OF    THE    BODY 

provided  with  organs,  or  sets  of  cells,  especially  differentiated 
for  maintaining  the  average  composition  of  this  fluid,  either  by 
taking  up  food  substances  from  the  surrounding  medium,  by 
the  transformation  of  these  foodstuffs,  or  by  discharging  into 
the  surrounding  medium  the  substances  which  would  tend  to 
accumulate  in  the  body  fluids  as  the  result  of  the  metabolism 
of  the  cells  of  the  body. 

This  process  of  excretion  is  in  nearly  all  animals  associated 
with  a  loss  of  fluid,  i.e.,  of  water,  to  the  organism.  Of  the 
metabolites  produced  as  the  result  of  chemical  changes  in  the 
tissues,  some,  such  as  CO2,  are  gaseous,  and  in  the  higher 
animals  are  excreted  through  the  lungs.  Others,  such  as  urea, 
are  solids,  and  can  be  got  rid  of  only  in  solution,  so  that  when 
they  leave  the  body  they  take  with  them  a  certain  amount  of 
water  as  well  as  of  salts.  Moreover,  in  animals  living  on  the 
earth's  surface,  evaporation  is  constantly  going  on  at  the  surface 
of  the  body,  and  in  man  this  evaporation  plays  a  prominent 
part  in  the  regulation  of  the  body  temperature,  i.e.,  in  creating 
a  constant  temj>erature  environment  for  the  cells  of  the  body. 

In  the  cell  processes  associated  with  activity  there  is  a 
breaking  down  of  complex  molecules  into  a  number  of  much 
smaller  and  simpler  molecules.  This  would  bring  about  an 
increase  in  the  molecular  concentration  of  the  body  fluids, 
were  it  not  that  any  excess  in  the  soluble  substances  in  these 
fluids  is  eliminated  in  a  concentrated  form  by  the  chief 
excretory  organs,  viz.,  the  kidneys. 

In  these  lectures  we  shall  not  concern  ourselves  with  the 
maintenance  of  the  food  supply  to  the  cells,  nor  to  any  large 
extent  with  the  removal  of  the  waste  products,  but  shall  devote 
our  attention  almost  exclusively  to  the  changes  in  the  water 
content  and  in  the  total  volume  of  the  fluids  of  the  body,  and 
with  the  manner  in  which  the  alimentary  canal  and  kidneys 
interact  for  the  maintenance  of  normal  conditions, 


THE    INTAKE    OF    FLUID  43 

The  intake  of  water,  and  probably  of  salts,  b}^  the  alimentary 
canal,  in  accordance  with  the  requirements  of  the  organism  as 
a  whole,  seems  to  be  regulated  almost  entirely  by  the  central 
nervous  system,  the  higher  j)arts  of  this  system,  viz.,  those 
concerned  with  appetite,  being  particularly  involved  in  the 
jDrocess.  Thus  in  man  any  large  loss  of  fluid,  as  by  sweating, 
diarrhoea,  or  haemorrhage,  gives  rise  to  an  intense  thirst  that  has 
its  natural  reaction  in  increased  intake  of  water  by  the  mouth. 
On  the  other  hand  the  property  possessed  by  the  alimentary 
canal  of  absorbing  water  and  weak  saline  fluids  contained  in 
its  interior  is  very  little  influenced  by  the  state  of  depletion,  or 
otherwise,  of  the  water  depots  of  the  bo(h\  Our  own  experience 
tells  us  that  it  is  practical)}'  impossible,  however  large  the 
quantities  of  fluid  that  we  ingest,  to  bring  about  the  produc- 
tion of  fluid  motions,  and  that  the  whole  of  the  ingested  fluid 
is  absorbed  on  its  way  through  the  alimentar}^  canal. 

Thus  a  man  may  keep  himself  in  perfect  health  and  main- 
tain the  water  contents  of  his  body  constant  whether  he  take 
two  pints  or  twelve  pints  of  water  daily.  The  whole  process  of 
regulation,  apart  from  that  determined  by  appetite,  appears  to 
be  carried  out  at  the  other  end  of  the  cycle,  viz.,  by  the  kidneys. 
As  concerns  absorption  of  water  there  is  no  chemical  solidarity 
between  the  alimentary  surface  and  the  rest  of  the  body. 
Whenever  water  is  presented  to  the  surface  it  is  absorbed  and 
passes  into  the  circulation. 

The  case  is  difterent  if  large  quantities  of  concentrated  saline 
fluid  be  ingested,  especially  if  the  salts  be  other  than  sodium 
chloride.  Certain  groups  of  salts  present  greater  resistance 
to  absorption  than  others  ;  among  them  we  may  mention  the 
tartrates  and  the  sulphates,  and  it  is  among  these,  therefore, 
that  our  chief  saline  purgatives  are  found.  But  in  every  case 
absorption  by  the  alimentary  surface  is  a  question  of  the  local 
conditions  rather  than  of  the  needs  of  the  organism  as  a  whole. 


44  THE    FLUIDS    OF    THE    BODY 

Only  in  extreme  hydraemic  plethora,  when  the  intestinal  ^Yall 
is  swollen  with  exuded  fluid,  may  we  observe  a  distinct 
hindering  of  the  process  of  absorption  or  actual  conversion 
of  absorption  into  secretion.  Such  a  condition  of  hj^drsemic 
plethora,  as  is  produced  in  animal  experiments  by  the  injection 
of  huge  quantities  of  normal  solution  into  the  circulation, 
probably  never  occurs  in  the  normal  intact  animal. 

In  this  lecture  we  have  to  discuss  the  nature  of  the  local 
conditions  in  the  alimentary  canal  which  determine  the 
absorption  of  water.  The  question  is  narrowed  by  the  fact, 
which  has  been  established  beyond  doubt  by  the  researches  of 
von  Mering,  Edkins  and  others,  that  the  absorj)tion  of  water 
in  the  stomach  may  be  regarded  as  nil.  Although  from  this 
viscus  alcohol,  peptone  and  sugar  may  be  absorbed  to  a  certain 
extent,  water,  or  saline  fluids  introduced  into  it,  are  passed 
through  the  pylorus  either  without  change,  or  with  their 
quantities  added  to  by  the  secretion  of  fluid  from  the  gastric 
glands.  In  no  case  is  there  a  diminution  of  fluid  in  the 
stomach. 

The  chief  absorption  of  water  occurs  in  the  small  intestine. 
It  is  on  this  account  that  the  salient  features  of  cases  of  dilata- 
tion of  the  stomach  with  stenosis,  absolute  or  relative,  of  the 
pyloric  orifice  can  be  nearly  all  referred  to  the  deprivation  of 
the  body  of  water,  and  can  often  be  relieved  by  the  administra- 
tion of  water  either  subcutaneously  or  by  the  rectum,  i.e.,  by 
the  channels  through  which  absorption  is  still  possible.  The 
introduction  of  water  into  the  stomach  simply  increases  the 
dilatation  but  does  not  relieve  the  intense  thirst  of  the  patient. 
Water  that  has  been  swallowed  to  quench  thirst  has  first  to  be 
passed  from  the  stomach  into  the  small  intestine  before  it  can  , 
be  absorbed  and  relieve  the  needs  of  the  tissues. 

A  certain  amount  of  absorption  of  water,  as  we  have  seen, 
may  occur  in  the  large  intestine.     The  intestinal  contents  at 


THE    INTAKE    OF    FLUID  45 

the  ileo-csecal  valve  contain  relatively  nearly  as  much  water 
as  they  do  at  the  upper  part  of  the  jejunum.  Their  absolute 
bulk  is  hoNvever  much  smaller,  so  that  only  a  small  propor- 
tion of  the  water  that  has  been  taken  in  by  the  mouth  remains 
to  be  absorbed  in  the  large  gut :  an  amount  probably  not  equal 
to  that  which  has  been  added  to  the  contents  of  the  small 
intestine  in  the  form  of  secretion  by  the  stomach,  liver, 
pancreas,  and  intestinal  tubules. 

The  problem  before  us  is  therefore  the  mechanism  of 
absorption  by  the  intestinal  villi.  The  injection  of  large 
quantities  of  water  or  normal  salt  solution  into  the  lumen  of 
the  small  intestine  hardly  affects  the  flow  of  lymph  from  the 
abdominal  cavity,  any  increase  in  flow  being  secondary  to  an 
increase  in  the  volume  of  the  circulating  blood.  The  passage 
of  fluid  from  the  gut  is  therefore  into  the  blood  vessels.  Inter- 
vening between  the  blood  vessels  and  the  gut  cavity  we  find 
only  the  layer  of  columnar  epithelial  cells  united  together  by 
a  certain  amount  of  cement  substance.  What  are  the  factors 
concerned  in  the  passage  of  the  fluid  across  this  epithelial 
layer  ?  The  movements  of  the  gut  and  the  movements  of  the 
blood  provide  for  practically  steady  composition  on  the  two 
sides  of  the  membrane,  so  that  we  have  to  enquire  whether 
the  physical  differences  between  the  fluid  on  one  side  and 
that  on  the  other  of  the  membrane,  taken  in  connection  with 
the  permeability  of  the  cell  membrane  itself,  are  suflicient  to 
account  for  the  up-take  of  water  and  salts. 

If  we  were  dealing  with  a  dead  colloidal  membrane,  such  as 
bladder,  p)archment  paper,  or  gelatin  (permeable  both  to 
water  and  salts),  it  would  be  easy  to  determine  the  conditions 
under  which  the  transference  of  fluid  from ,  one  side  to  the 
other  may  take  place.  In  such  a  case  the  passage  of  water 
would  depend  on  the  relative  molecular  concentration  on  the 
two  sides  of  the  membrane,  on  the  relative  diffusibility  through 


46 


THE    FLUIDS    OF    THE    BODY 


the  membrane  of  the  salts  on  the  two  sides,  as  well  as  on  the 
presence  on  the  one  side  or  other  of  constituents  in  solution,  or 
semi-solution,  e.g.,  colloids,  to  which  the  membrane  was  imper- 
meable. Thus,  in  the  case  of  two  solutions  A  and  B  separated 
by  such  a  membrane,  if  the  osmotic  pressure,  or  molecular 
concentration,  of  B  be  higher  than  A,  the  force  tending  to 
move  water  from  A  to  B  will  be  equal  to  this  osmotic 
difference.  There  is  at  the  same  time  set  up  a  diffusion  of  the 
dissolved  substances  from  B  to  A  and  from  A  to  B.  The 
result  of  this  diffusion  must  be  that  there  is  no  longer  a 
sudden  drop  of  osmotic  pressure  from  B  to  A,  and  the  result 
of  the  primary  osmotic  difference  on  the  movement  of  water 


111 


A 

B 

Fig.  2. 

will  be  minimised  in  proportion  to  the  freedom  of  diffusion 
which  takes  place  through  the  membrane.  Now  let  us  take 
a  case  in  w^hich  A  and  B  represent  equimolecular  and  isotonic 
solutions  of  a  and  13.  It  is  evident  that  the  movement  of 
water  into  A  will  vary  as  Ap  —  Bp*  =  0.  But  diffusion  also 
occurs  of  a  into  B  and  of  jS  into  A.  Now  the  amount  of 
substance  diffusing  from  a  solution  is  proportional  to  the  con- 
centration, and  therefore  to  its  osmotic  pressure,  as  well  as  to 
its  diffusion  coefficient. 

Hence  the  amount  of  a  diffusing  into  B  will  vary  as  Ap. 
ak  (when  k  is  the  diffusion  coefficient). 

In  the  same  way  the  amount  of  B  diffusing  into  A  will  vary 
as  Bp,  ;8k^ 

*  Ap  =  osmotic  pressure  of  A,  etc. 


THE    INTAKE    OF    FLUID  47 

Hence  if  ak  is  greater  than  /3k^,  i.e.,  if  a  is  more  diffusible 
than  l3,  the  initial  result  must  be  that  a  greater  number  of 
molecules  of  a  will  pass  into  B  than  of  /3  into  A.  Hence  the 
solutions  on  the  two  sides  of  the  membrane  will  be  no  longer 
equimolecular,  but  the  total  number  of  molecules  of  a  -f  ^  in 
B  will  be  greater  than  the  number  of  molecules  of  a  +  /3  in 
A,  and  this  difference  will  be  most  marked  in  the  layers  of 
fluid  nearest  the  membrane.  The  result  therefore  of  the 
unequal  diffusion  of  the  two  substances  is  to  upset  the  previous 
equality  of  osmotic  pressures.  The  layer  of  fluid  on  the  B 
side  of  the  membrane  will  have  an  osmotic  pressure  greater 
than  the  layer  of  fluid  in  immediate  contact  with  the  A  side  of 
the  membrane,  and  there  will  thus  be  a  movement  of  water 
from  A  to  B.  Hence,  if  we  have  two  equimolecular  and 
isotonic  solutions  of  different  substances  separated  by  a 
membrane  permeable  to  the  dissolved  substances,  there  will 
be  an  initial  movement  of  fluid  towards  the  side  of  the  less 
diffusible  substance. 

We  have  an  exact  parallel  to  this  in  Graham's  familiar 
experiment  in  which  a  porous  pot  filled  with  hydrogen  is  con- 
nected by  a  vertical  tube  with  a  vessel  containing  mercury. 
In  consequence  of  the  more  rapid  diffusion  of  the  hydrogen 
outwards  than  of  atmospheric  air  inwards,  the  pressure 
within  the  pot  sinks  below  that  of  the  surrounding  atmo- 
sphere, and  the  mercury  rises  several  inches  in  the  tube. 
We  must  therefore  conclude  that,  even  when  the  two  solu- 
tions on  either  side  of  the  membrane  are  isotonic,  there  may 
be  a  movement  of  fluid  from  one  side  to  the  other  with  a 
performance  of  work  in  the  process. 

Indeed,  as  w^as  shown  by  Lazarus-Barlow,*  osmosis  may 
occur   from  a  fluid   having  a  higher  final  osmotic  pressure 

*  Lazarus -Barlow.     Journ.  of  Physiol.,  XIX.,  p.  140.     1895. 


48  THE    FLUIDS    OF    THE    BODY 

towards  a  fluid  having  a  lower  final  osmotic  pressure.  If,  for 
example,  enuimolecular  solutions  of  sodium  chloride  and 
glucose  be  separated  by  a  peritoneal  membrane,  the  osmotic 
flow  will  take  place  from  the  fluid  having  the  higlier  final 
osmotic  pressure — viz.,  the  sodium  chloride.  We  might  com- 
pare with  this  experiment  the  results  of  separating  hydrogen 
at  one  atmosphere's  pressure  from  oxygen  at  two  atmospheres' 
pressure  by  means  of  a  plate  of  graphite.  In  this  case  the 
initial  result  will  be  a  still  further  increase  of  pressure  on  the 
oxygen  side  of  the  diaphragm — a  movement  of  gas  against 
pressure  taking  place  in  consequence  of  the  greater  diffusion 
velocity  of  hydrogen. 

So  far  we  have  only  considered  the  behaviour  of  solutions 
when  separated  by  a  membrane,  the  permeability  of  which  to 
salts  is  comparable  to  that  of  water ;  so  that  the  piassage  of 
salts  through  the  membrane  depends  merely  on  the  diffusion 
rates  of  the  salts.  There  can  be  no  doubt,  however,  that  we 
might  get  analogous  movements  of  fluid  against  total  osmotic 
pressure  determined,  not  by  the  diffusibility  of  salts,  but  by 
the  permeability  of  the  membrane  to  the  salts — a  ^permeability 
which  may  depend  on  a  state  of  solution  or  attraction  existing 
between  membrane  and  salts.  We  have  a  familiar  analogue 
to  such  a  condition  of  things  in  the  j)assage  of  gases  through 
an  india-rubber  sheet.  If  two  bottles,  one  containing  carbonic 
acid,  the  other  hydrogen,  be  separated  by  a  sheet  of  india- 
rubber,  CO2  passes  into  the  hydrogen  bottle  more  quickly  than 
hydrogen  can  pass  out  into  the  CO2  bottle,  so  that  a  difference 
of  pressure  is  created  between  the  two  bottles,  and  the  rubber 
bulges  into  the  CO2  bottle.  We  might,  in  the  same  way,  con- 
ceive of  a  membrane  which  permitted  the  passage  of  dextrose 
more  easily  than  that  of  sodium  chloride.  With  such  a  mem- 
brane, experiments  conducted  in  the  same  way  as  Dr.  Barlow's 
would    lead    to    the    diametrically    oj)posite   results.      The 


THE    INTAKE    OF    FLUID  49 

importance  of  the  membrane  in  determining  the  direction 
of  the  osmotic  passage  of  fluid  is  well  illustrated  by  Raoult's 
experiments  mentioned  in  the  first  lecture.  When  alcohol 
and  ether  were  separated  by  an  animal  membrane,  alcohol 
passed  into  the  ether,  whereas  if  vulcanite  were  emj^loyed 
for  the  diaphragm,  the  osmotic  flow  was  in  the  reverse  direc- 
tion, and  an  enormous  pressure  was  set  up  on  the  alcohol 
side  of  the  diaphragm. 

The  next  point  to  be  considered  is  the  passage  of  a  dissolved 
substance  across  membranes  in  consequence  of  differences  in 
the  partial  pressure  of  the  substance  on  the  two  sides  of  the 
membrane.  Great  stress  was  laid  by  Heidenhain  and  his 
pupil  Orlow  on  the  fact  that  in  the  peritoneal  cavity,  as 
well  as  from  the  intestine,  sodium  chloride  may  be  taken 
up  from  fluids  containing  a  smaller  percentage  of  this  sub- 
stance than  does  blood-plasma ;  and  they  regard  this  absorp- 
tion as  pointing  indubitably  to  an  active  intervention  of  living 
cells  in  the  process.  This  argument  requires  examination. 
Supposing  the  two  vessels  A  and  B  to  be  separated  by  a 
membrane  which  offers  free  passage  to  water,  and  a  difficult 
passage  to  salts.     Let  A  contain  '5  per  cent,  salt  solution  and 


B 


B  a  solution  isotonic  with  a  1  per  cent.  NaCl,  but  containing 
only  '65  per  cent,  of  this  salt,  the  rest  of  its  osmotic  tension 
being  due  to  other  dissolved  suhsta7ices.  If  the  membrane  were 
absolutely  'semi-permeable,'  water  would  pass  from  A  to  B 
until  the  two  fluids  were  isotonic,  i.e.,  until  A  contained  1  per 
cent.  NaCl  (to  simplify  the  argument  we  may  regard  volume 
B  as  infinitely  greater).     If  however  the  membrane  permitted 

F.B.  E 


50  THE   FLUIDS    OF    THE    BODY 

passage  of  salt,  the  course  of  events  might  be  as  follows  : 

At  first  water  would  pass  out  of  A  and  salt  would  diffuse  in 
until  the  percentage  of  NaCl  in  A  was  equal  to  that  in  B. 
There  would  not  be  an  equal  partial  pressure  of  NaCl  on  the 
two  sides  of  the  membrane,  but  the  total  osmotic  pressure  of 
B  would  still  be  higher  than  A.  Water  would  therefore  still 
continue  to  pass  from  A  to  B  more  rapidly  than  the  other 
ingredients  of  B  could  pass  into  A.  As  soon  however  as 
more  water  passed  only  from  A,  the  percentage  of  NaCl  in  A 
would  be  raised  above  that  in  B.  The  extent  to  which  this 
occurs  will  depend  on  the  impermeability  of  the  membrane. 
When  the  NaCl  in  A  reaches  a  certain  concentration,  it  will 
pass  over  into  B,  and  this  will  go  on  until  equilibrium  is 
established  between  A  and  B.  Extending  this  argument  to 
the  conditions  obtaining  in  the  living  body,  we  may  conclude 
that  neither  the  raising  of  percentage  of  a  salt  in  a  fluid 
above  that  of  the  same  salt  in  the  plasma,  nor  the  passage 
of  a  salt  from  a  hypotonic  fluid  into  the  blood-plasma,  can 
afford  in  itself  any  proof  of  an  active  intervention  of  cells  in 
the  process. 

We  have  already  seen  that  the  effective  osmotic  pressure  of 
a  substance,  i.e.,  its  power  of  attracting  water  across  a  mem- 
brane, varies  inversely  as  its  diffusibility,  or  as  the  permea- 
bility of  the  membrane  to  it.  What  will  be  the  effect, 
supposing  that  on  one  side  of  the  membrane  we  place 
some  substance  in  solution  to  which  the  membrane  is 
impermeable  ? 

We  will  suppose  that  A  and  B  contain  1  per  cent.  NaCl, 
but  that  B  contains  in  addition  some  substance  x  to  which  the 
membrane  is  impermeable.  Since  the  osmotic  pressure  of  B 
is  higher  by  the  partial  pressure  of  x  than  that  of  A,  fluid 
will  pass  from  A  to  B  by  osmosis.  But  the  consequence  of 
this  passage  of  water  will  be  to  concentrate  the  NaCl  in  A,  so 


THE    INTAKE    OF    FLUID  51 

that  the  partial  pressure  of  this  salt  in  A  is  greater  than  in  B. 
NaCl  will  therefore  diffuse  from  A  to  B  with  the  result  that 
the  former  difference  of  total  osmotic  pressure  will  be  re-estab- 
lished. Hence  there  will  be  a  continual  passage  of  both  water 
and  salt  from  A  to  B,  until  B  has  absorbed  the  whole  of  A. 
This  result  will  be  only  delayed  if  the  osmotic  pressure  of  A  is 
at  first  higher  than  B,  in  consequence  of  a  greater  concentra- 
tion of  NaCl  in  A.  There  may  be  at  first  a  flow  of  fluid  from 
B  to  A,  but  as  soon  as  the  NaCl  concentration  on  the  two 
sides  has  become  the  same  by  diffusion,  the  power  of  x  to 
attract  water  from  the  other  side  will  make  itself  felt,  and 
this  attraction  will  be  proportional  to  the  osmotic  pressure 
of  X. 

In  the  case  of  the  intestinal  cell,  the  substance  x  may  be 
represented  by  the  colloids  of  the  blood-plasma  circulating  in 
the  capillaries,  which,  as  I  have  shown,*  have  a  definite 
'  osmotic  pressure '  or  attraction  for  water  equivalent  to 
about  30  mm.  Hg.,  and  this  minimal  attraction  would  in  time 
determine  the  transference  of  the  whole  of  the  saline  fluid 
from  the  lumen  of  the  gut  to  the  blood  vessels. 

The  question  how  far  these  conditions  for  physical  absorp- 
tion are  fulfilled  in  the  case  of  the  intestine  must  be  deter- 
mined by  actual  experiment  on  the  living  animal.  We  know 
already  something  about  the  permeability  of  the  epithelial 
membrane  lining  the  intestine.  Like  all  other  cells  of  the 
body,  the  free  surface  of  the  intestinal  cells  can  be  regarded 
as  probably  lipoid  in  character  and  therefore  physically 
permeable  only  by  such  substances  as  are  soluble  in  such 
a  membrane,  e.g.,  by  water,  by  alcohols,  urea,  and  other 
substances  enumerated  in  my  previous  lecture. 

The  permeability  of  the  cement  substances  between  the  cells 

*  Joiirn.  of  Physiol.,  XIX.,  312,  1896. 

E    2 


52  THE    FLUIDS    OF    THE    BODY 

may  possibly  be  assumed  as  having  a  wider  scope.  If  the 
permeability  of  the  intestinal  wall  can  be  deduced  from  this 
analogy  with  other  cells  of  the  body,  such  as  red  corpuscles, 
we  may  assume  that  the  main  foodstuffs,  e.g.,  sugar,  as  well 
as  all  the  salts,  can  only  obtain  entrance  into  the  interior  of 
the  villus  by  the  inter-epithelial  spaces,  while  through  the  cells 
only  such  substances  can  be  absorbed  as  are  soluble  in  lipoid 
media. 

Let  us  see  how  far  these  generalisations,  which  have  been 
the  theme  of  investigation  chiefly  by  Hober,*  bear  the  test  of 
experiment. 

When  the  paths  of  absorption  are  studied  by  the  histo- 
logical examination  of  the  wall  of  the  gut  after  the  administra- 
tion of  various  dyes,  only  such  dyes  as  are  soluble  in  lipoids 
are  found  in  the  cells  lining  the  intestine,  where  they  accumu- 
late in  a  granular  form.  Since  the  dyes  not  soluble  in  lipoids, 
such  as  indulin,  are  absorbed  into  the  system  from  the  ali- 
mentary canal,  and  yet  cannot  be  traced  through  the  cells, 
Hober  concludes  that  they  pass  by  means  of  the  inter- 
epithelial  cement-substance  in  a  highly  dilute  condition. 
None  of  these  dye  substances  can  be  regarded  however  as 
normal  foodstuffs,  or  as  arousing  in  any  way  the  normal 
functions  of  the  alimentary  mucous  membrane,  and  consider- 
able difficulties  are  met,  if  we  attempt  to  draw  conclusions 
from  these  experiments  regarding  the  path  normally  taken  by 
such  constituents  of  the  food  as  salts,  sugar,  or  amino-acids. 
Dextrose,  for  instance,  is  absorbed  with  great  rapidity  by  the 
small  intestine,  especially  in  the  upper  reaches  of  the  gut. 
Cane-sugar  is  also  absorbed,  but  more  slowly,  and  undergoes 
inversion  in  the  process.     This  difference  in  absorbability  of 

''•  See  a  full  account  of  this  work  in  Hober' s  article  in  the  "  Handbuch 
der  Physikaliscken  Chemie  in  der  Medi^in  "  (Koranyi  and  Bitter),  p.  328. 


THE    INTAKE    OP    FLUID  53 

mono-  and  di-  saccharide  might  be  referred  to  their  varying 
diffusibihties,  were  it  not  that  another  closely-related  di- 
saccharide,  viz.,  lactose,  is  not  absorbed  at  all,  except  in  such 
animals  as  i)ossess  the  ferment,  lactase,  in  their  intestinal 
wall.  In  other  animals  lactose  acts  as  a  pm'gative,  and  even 
in  man  large  doses  of  this  sugar  has  a  laxative  action,  owing 
to  the  slowness  with  which  it  undergoes  inversion  in  the 
intestine.  It  is  difficult  to  account  for  these  differences 
between  the  absorbabihties  of  various  sugars,  so  long  as  we 
locate  the  path  of  their  absorption  in  the  inert  dead  cement- 
substance  between  the  epithelial  cells. 

Similar  difficulties  meet  us  when  we  attemj)t  to  account  for 
the  behaviour  of  saline  solutions  introduced  into  the  cavity  of 
the  gut.  If  the  solutions  contain  sulj^hates  or  tartrates,  i.e., 
salts  to  whose  anions  the  gut-wall  is  relatively  imj)ermeable, 
the  course  of  events  is  very  much  the  same  as  that  which 
would  occur  if  these  solutions  were  separated  from  blood- 
plasma  by  a  dead  wall  of  parchment  paper.  If  they  are 
hypertonic,  they  increase  in  amount  by  the  attraction  of  water 
from  the  circulating  fluids,  until  their  molecular  concentration 
is  equal  to  that  of  the  blood-plasma.  If  however  they  remain 
in  the  gut  for  a  considerable  time,  they  are  finally  absorbed, 
just  as  they  would  be  from  a  tube  of  parchment  paper.  This 
final  absorption  could  be  ascribed  to  the  colloids  of  the  blood 
serum.  Very  difterent  is  the  fate  of  solutions  of  substances 
such  as  sodium  chloride.  These  are  rapidly  absorbed  even 
when  they  are  slightly  hypertonic.  If  the  solutions  are  strong, 
i.e.,  2  to  3  per  cent.  NaCl,  they  may  at  first  increase  in  bulk 
by  the  diffusion  of  water  into  them.  From  the  moment  of 
their  introduction  however,  salt  is  passing  from  them  into  the 
blood  circulating  through  the  intestinal  wall,  and  as  soon  as 
their  total  osmotic  pressure  is  reduced  to  a  point  a  little  above 
that  of  the    blood-plasma,  both  water  and  salt  begin  to  be 


54 


THE    FLUIDS    OF    IUE   BODY 


absorbed.  It  might  be  possible  in  an  individual  case,  by 
juggling  with  the  factors  that  I  have  previously  discussed,  to 
explain  the  final  absorption  even  of  solutions  of  sodium 
chloride.  To  do  this  however,  we  have  to  ascribe  to  the 
membrane  clothing  the  intestine  a  property  to  which  we  have 
no  analogue  in  any  known  dead  membrane,  viz.,  an  irreciprocal 
permeability  for  NaCl.  Although  sodium  chloride  passes 
with  the  greatest  ease  from  the  lumen  of  the  gut  into  the 
blood  vessels,  considerable  resistance  is  offered  to  its  passage 
in  the  reverse  direction.  The  small  amounts  which  actually 
pass  from  the  blood  into  the  gut,  e.g.,  into  an  isotonic  solution 
of  glucose,  may  be  entirely  attributed  to  a  minimal  secretion 
of  succus  entericus.  This  irreciprocal  permeability  is  bound 
up  with  the  life  of  the  cells  covering  the  mucous  membrane, 
and  is  at  once  abolished  if  these  cells  be  damaged  by  the 
addition  of  small  amounts  of  NaF  to  the  fluid  introduced  into 
the  gut,  or  by  the  action  of  distilled  water  or  of  temporary 
anaemia.  Under  these  circumstances  the  rapid  absorption  of 
solutions  of  sodium  chloride  is  abolished,  and  the  changes  in 
the  volume  and  concentration  of  the  fluid  introduced  into  a 
loop  of  gut  are  apparently  determined  entirely  by  its  molecular 
concentration. 

The  irreciprocal  permeability  of  the  intestinal  wall  to  NaCl 
is  well  shown  in  the  following  exj)eriment  by  Waymouth 
Eeid.* 

Dog.     18  kilos.     Two  40-centimetre  loops  of  ileum  in  continuity. 
Duration  of  experiment,  15  minutes. 


Introduced 


Upper  Loop. 


30  cub.  centims.  of  5 "74  jDer 
cent,  solution  of  glucose. 


Lower  Loop. 


'SO  cub.  centims.  of  distilled 
water. 


-  Fhil.  Tians.,  B.,  CXCII.,  211,  1900. 


THE    INTAKE    OF   FLUID 


55 


Water. 


— 

Recovered. 

Absorbed, 

Absorbed  in  per  cent,  of  introduced. 

Glucose  loop 
Water  loop     .  . 

cub.  centims. 
28 
18 

cub.  centims. 
2 
12 

per  cent. 

6-67 
40-00 

Sodic  Chloride  added  from  Blood. 
Glucose  loop  .  .    *016  grm.,  i.e.,  'Ool  per  cent,  in  fluid  in  gut  at  end  of 

experiment 
Water  loop..  ..    "OoS        „  '322        ,,         ,,  ,,  ,, 

Glucose  absorbed  .  .    -420        „      24*4  ,, 

Hence  more  than  three  times  as  much  sodic  chloride  entered 
the  water  than  the  glucose  solution  from  the  blood  owing  to 
the  injurious  effect  of  the  distilled  water  on  the  cells. 

Moreover  we  have  distinct  evidence  that  the  vitality  of  the 
cells  involves,  not  merely  a  passive  preservation  of  an  irrecipro- 
cal permeability,  but  also  an  active  transference  of  water  from 
one  side  to  the  other  of  the  membrane.  Waymouth  Reid  has 
shown  that,  if  the  animal's  own  serum  be  introduced  into  a 
loop  of  its  intestine,  it  undergoes  absorption.  This  absorption 
affects  the  water  and  salts  more  than  the  protein,  so  that  the 
percentage  of  the  proteins  in  the  fluid  remaining  in  the  intes- 
tine is  increased.  In  this  case  the  fluid  within  the  gut  is 
identical  with  the  fluid  within  the  blood  vessels.  There  are 
no  differences  in  concentration,  quality  of  salts,  or  osmotic 
pressure  of  proteins.  Nevertheless,  water  passes  through  the 
cells  of  the  gut  from  their  inner  to  their  outer  sides,  entraining 
with  it  the  salts  of  the  serum  and  a  certain  proportion  of  the 
indiflusible  proteins.  Any  digestive  changes  in  the  proteins 
as  a  preliminary  to  absorption  can  be  excluded  by  the  facts 
that,  in  these  experiments,  the  intestinal  loops  were  washed 
free  of  any  trypsin  that  they  contained,  and  that  serum  itself 
has  a  strong  antitryptic  action  which  would  prevent  its  being 
attacked  by  even  a  strong  solution  of  trypsin. 


56 


THE    FLUIDS   OF   THE   BODY 


The  following  two  experiments  bring  out  clearly  the  facts 
discussed  in  the  foregoing  paragraph  : — 

Absorption  of  Serum  trom  Intestine  (W.  Eeid). 

Dog.  16  kilos.  Two  80-centimetre  loops  of  ileum.  Duration  of  experi- 
ment,  ^  hour.  Mesenteric  vessels  of  one  loop  clamped  for  20  minutes 
previous  to  experiment.     Grreat  detachment  of  epitheHum. 


Organic  solids. 

Salts. 

grms. 

grm. 

Introduced  into  each  loop  50  cub.  centims.  of 

own  serum,  holding  .  . 

3-2465 

•4735 

Eecovered:    Normal  loop,  35  cub.  centims. 

' 

of  serum,  holdins: 

2-4847 

•3188 

,,           Previously  anaemic  loop,  48  cub. 

centims.  of  serum,  holding    .  . 

2-9573 

•4507 

Ahsorhed  in  i  hour. 


Normal  loop. 


Water  .  .  15-00  cub.  centims.,  t.e. 

Organic  solids      -7618  grm.  ,, 

Salts  .  .  . .       -1547     ,,  ,, 


per  cent. 

30-00 
23-46 
32-67 


Previously  anse.mic  loop. 


per  cent. 

2  cub.  centims.,  i.e.  4*00 
•2892  grm.  ,,  8-90 
•0228  grm.        „    4-81 


Absorption  of  Serum  from  Intestine  (W.  Eeid). 

Dog.  23-5  kilos.  Two  80-centimetre  loops  of  ileum.  Duration  1  hour. 
One  loop  washed  with  '8415  per  cent,  solution  of  sodic  chloride, 
holding  "1  jDcr  cent,  of  sodic  fluoride,  the  other  with  -9804  per  cent, 
solution  of  sodic  chloride.     Lowering  of  freezing  point  of  each  wash 

=  -  -590'=  0. 


Organic  solids. 

Salts. 

grms. 

grm. 

Introduced  into  each  loop  50  cub.  centims.  of 

own  serum,  holding  .  . 

3-6050 

•4550 

Eecovered :  Normal  Ioojd,   20   cub.    centims. 

serum,  holding 

1-8740 

•1720 

,,           Fluoride-washed    loop,    50  cub. 

centims.  serum,  holding 

3-3700 

•4700 

THE    INTAKE    OF    FLUID 


57 


Absorbed  in  one  Jiour. 


Water 

Organic    solids 
Salts    . . 


Normal  loop. 


per  cent. 

30-00  cub.  centims.,  i.e.  6000 

1-7310  grm.  ,,    48*01 

•2830     „  „    62-19 


Fluoride-washed  loop. 

per  cent. 

0-00  cub.  centim.,  i.e.  0-00 
-235  grm.  ,,    6-52 

•015     ,,  (added)    ,,    3-30 


Hydrostatic  Pressures. 

Normal  loop  . .  . .     7  to  1 1  millims.  of  Hg. 

Fluoride -washed  loop.  .  .  .     9  to  12         ,,  ,, 


Lowering  of  Freezing  Point. 

Introduced  serum. 

Removed  from 
fluoride  loop. 

Removed  from 
normal  loop. 

Serum  of  dog  at  end 
of  experiment. 

-  -eoo^c. 

-  -630°C. 

-  -560°C. 

-  -640°C. 

The  epithelial  cells  of  the  intestine  must  therefore  be  actively 
involved  in  the  absorption  of  fluid,  ?.^.,  a  certain  proportion  of 
the  energy  set  free  within  them  by  the  oxidation  of  their  food- 
stuffs must  be  employed  in  the  pumping  of  water  and  salts 
from  one  side  of  the  cell  to  the  other.  This  conclusion  is 
confirmed  by  certain  experiments  of  Eeid*  and  Cohnheim,f  in 
which  two  identical  solutions  of  sodium  chloride  were  separated 
from  one  another  by  a  membrane  consisting  of  the  whole  living 
intestinal  wall.  In  these  experiments  it  was  found  that  there 
was  active  transference  from  the  inner  to  the  outer  side  of  the 
membrane. 

We  must  conclude  that,  when  a  fluid  is  introduced  into  the 
intestine,  an  active  transference  of  water  from  the  lumen  into 
the  blood-stream  is  effected  by  the  intermediation  of  forces 
having  their  origin  in  the  metabolism  of  the  cells  themselves. 


-  E.  W.  Eeid,  Jouru.  of  Physiol.,  XXYL,  436,  1901. 
t  Cohnbeim,  Ztsch.  f.  Biol.,  XXXYIII.,  419,  1899.. 


58  THE    FLUIDS   OF   THE    BODY 

This  work  of  absorption  may  be  aided  or  hindered  according 
to  the  physical  conditions  present.  If  these  act  against  the 
cells,  e.g.,  if  the  fluid  be  hypertonic,  the  absorption  is  effected 
more  slowly,  while  with  hypotonic  solutions,  the  physical  con- 
ditions concur  with  the  vital  activity  of  the  cells  in  bringing 
about  a  very  rapid  transference  of  fluid  from  the  gut  into  the 
blood  vessels.  Among  these  physical  conditions,  we  must 
reckon  the  nature  of  the  salts  present  in  the  solution.  If 
these  can  pass  easily  into  and  through  the  cells,  e.g., 
ammonium  salts,  sodium  chloride,  absorption  is  carried  out 
rapidly.  If,  on  the  other  hand,  the  salts  in  the  intestinal 
contents  are  but  slightly  diffusible  or  have  very  little  power  of 
penetrating  into  the  cells,  the  absorption  of  water  by  the  cells 
causes  an  increased  concentration  of  the  salts,  and  therefore 
an  increased  osmotic  pressure,  which  offers  a  resistance  to  any 
further  absorption  ;  and  the  process  comes  to  an  end,  when  the 
absorptive  power  of  the  cells  is  exactly  balanced  by  the 
increased  osmotic  pressure,  or  attraction  for  water,  of  the 
intestinal  contents. 

We  must  therefore  ascribe  absorption  of  fluids  by  the  intes- 
tines to  the  activity  of  the  cells  clothing  the  villi.  The 
effectiveness  of  this  activity  will  be  influenced  by  the  osmotic 
pressure  and  the  quality  of  the  solutions  involved,  just  as  the 
results  of  the  contractions  of  our  muscles  will  differ  according 
to  the  resistance  which  the  contractions  have  to  overcome. 

Very  similar  problems  to  those  presented  by  the  intestinal 
epithelium  engage  our  attention  when  we  investigate  the 
exchanges  of  fluid  through  the  frog's  skin.  Under  normal 
circumstances  the  frog  can  take  in  water  through  its  integu- 
ment in  the  same  way  as  man  can  absorb  through  his  intestine. 
If,  for  instance,  a  frog  be  poisoned  with  curare  and  be  placed 
in  a  vessel  with  a  little  water,  it  is  noticed  at  the  end  of  twenty- 
four  hours  that  the  frog  has  become  dropsical.     The  action  of 


THE    INTAKE    OF    FLUID  69 

curare  has  been  to  modify  the  permeability  of  the  capillaries 
so  as  to  affect  the  balance  between  the  production  and  absorp- 
tion of  tissue  fluid  in  the  direction  of  increased  transudation. 
The  water  lost  to  the  blood  in  this  way  is  taken  up  by  the 
frog's  skin. 

A  very  accurate  series  of  observations  was  carried  out  by 
Waymouth  Eeid  *  on  the  factors  determining  the  movement  of 
fluid  through  the  skin.  He  first  showed  that  the  skin,  like 
the  intestinal  mucous  membrane,  presents  a  certain  amount 
of  irreciprocal  permeability,  as  evidenced  by  the  fact  that  the 
diffusion  of  water  into  or  out  of  various  solutions  differs 
according  as  the  movement  is  from  within  outwards,  or  from 
without  in.  He  then  investigated  the  behaviour  of  the  skin 
w^hen  it  was  used  as  a  diaphragm  separating  two  identical 
solutions  of  normal  sodium  chloride.  In  this  case  there  was 
distinct  passage  of  fluid  from  the  outer  to  the  inner  side  of  the 
skin — a  transference  which  could  be  explained  only  on  the 
hypothesis  that  work  was  done  on  the  fluid  by  the  cells  of  the 
skin  itself.  That  the  energy  of  this  work  was  derived  from 
the  normal  metabolism  inseparable  from  the  life  of  the  cells 
was  proved  by  adding  sodium  fluoride,  or  other  deleterious 
substance,  to  the  fluid  used  in  the  experiment,  when  the  cell 
behaved  like  ordinary  dead  membrane,  the  irreciprocal 
permeability  and  the  active  transference  of  fluid  totally 
disaj)pearing. 

We  may  conclude  therefore  that  the  intake  of  fluid  occurs 
for  the  greater  part  in  the  small  intestine.  The  presence  of 
fluid  in  the  lumen  of  the  gut  gives  rise  to  a  stream  of  water 
from  the  gut  into  the  circulating  blood,  brought  about  by  the 
activity  of  the  cells  clothing  this  viscus,  i.e.,  by  the  force  set 
free  in  the  normal  metabolism  of   these  cells.     This  active 

-  E.  W.  Eeid,  Journ.  of  Physiol.,  XI.,  312,  1890. 


60  THE    FLUIDS    OF    THE    BODY 

absorption  may  be  aided  or  opposed  by  the  ordinary  osmotic 
factors  at  work,  which  depend  on  the  concentration  of  the 
fluid  introduced  into  the  gut  and  on  the  nature  of  the 
dissolved  salts. 

Thus  if  the  solutions  contain  salts,  such  as  sodium  chloride 
or  salts  of  ammonia,  which  pass  easily  through  the  mucous 
membrane,  the  absorption  of  the  fluid  is  rapidly  carried 
out.  If,  on  the  other  hand,  salts,  such  as  sodium  sulphate, 
which  pass  with  extreme  difficulty  through  the  cell  lining,  are 
present,  the  osmotic  pressure,  due  to  the  dissolved  salts,  con- 
tinues as  a  force  opposing  the  absorptive  activity  of  the  cells. 
Water  may  be  absorbed  u-p  to  a  certain  point,  viz.,  until  the 
surplus  of  the  molecular  concentration  of  the  salt  solution 
over  that  of  the  blood-plasma  produces  an  osmotic  pressure 
or  attraction  for  water  which  exactly  counterbalances  the 
absorbing  forces  of  the  intestinal  epithelium.  It  is  not 
surprising  therefore  that  many  authors  have  found  that  the 
rate  of  absorption  of  any  saline  solution  is  proportional  to  the 
diffusibility  of  the  salts  they  contain. 

When  serum  is  introduced  into  the  gut,  the  stream  of  water 
carries  with  it  both  the  dissolved  salts  and  the  dissolved  pro- 
tein. In  the  case  of  the  latter  however,  there  is  a  certain  lag, 
so  that  the  fluid  becomes  more  and  more  concentrated  in 
protein,  until  the  intestinal  contents  become  almost  solid, 
and  absorj)tion  ceases  until  the  serum  j)rotein  can  be  broken 
up  by  the  digestive  ferments  of  the  gut.  Whether  there  is 
an  active  absorption  of  dissolved  substances  apart  from  water 
cannot  yet  be  regarded  as  distinctly  settled,  though  the  different 
rates  at  which  the  various  sugars  are  dissolved,  as  well  as 
the  uTeciprocal  permeability  of  the  membrane  for  sodium 
chloride,  point  to  the  fact  that  the  cells  of  the  intestine, 
besides  their  attraction  for  water,  have  the  power  of  picking 
up  out  of  the  intestinal  contents  those  substances  in  solution 


THE    INTAKE    OF    FLUID  61 

which   represent   the   normal   foodstuffs   of   all   the   cells  of 
the  body. 

With  this  selection  of  substances  the  adaptive  powers  of  the 
intestinal  epithelium  are  exhausted.  It  has,  if  we  may  so 
express  it,  little  or  no  feeling  of  the  needs  of  the  body  as  a 
whole,  and  the  satisfaction  of  these  needs  has  therefore  to  be 
provided  for  by  the  co-operation  of  the  central  nervous  system, 
including  those  higher  parts  of  this  system  which  are  involved 
in  the  production  of  appetite. 


LECTUEE  IV 

THE  EXCHANGE  OF  FLUIDS  IN  THE  BODY THE  PRODUCTION 

OF  LYMPH 

Under  the  term  internal  media  of  the  body  we  include 
three  distinct  fluids,  all  of  which  may  be  regarded  as  derived 
from  the  original  coelomic  fluid.     These  are  : — 

(1)  The  circulating  blood,  contained  in  a  closed  system 

of  tubes  and  everywhere  separated  from  the  tissues 
by  a  layer  of  endothelium. 

(2)  The   lymph,  also  contained    in    a    closed    system   of 

endothelial  tubes  connected  at  one  or  more  points 
with  the  blood  vascular  system. 

(3)  The  tissue  fluid,  filling  all  the  spaces  of  the  body  and 

in  immediate  contact  with  the  tissue  cells. 

This  last-named  is  the  real  internal  medium  of  the  body, 
into  which  the  cells  discharge  their  waste  products,  and 
from  which  they  derive  their  sustenance  as  well  as  their 
necessary  oxygen. 

In  considering  the  factors  which  determine  the  fluid 
exchanges  of  the  cells,  the  composition  and  amount  of  the 
tissue  fluid  are  therefore  of  extreme  importance.  Moreover 
we,  as  medical  men,  are  especially  interested  in  the  quantita- 
tive relationships  of  this  fluid,  since  on  this  depends,  under 
certain  pathological  conditions,  the  production  of  anasarca 
or  dropsy. 

Unfortunately  an  investigation  of  the  tissue  fluids  is  very 
much  more  difficult  than  is  the  case  with  the  blood  or  lymph. 
We  may  say,  as  a  general  rule,  that  increased  tissue  fluid  will 


EXCHANGE  OF  FLUIDS  IN  THE  BODY PRODUCTION  OF  LYMPH   63 

tend  to  produce  a  more  abundant  lymph  outflow  from  the 
part,  but  we  cannot  predicate  any  direct  proportionality 
between  these  two  phenomena.  Up  to  the  present  I  know 
of  only  two  sets  of  researches  dealing  with  the  amount  of 
tissue  fluid  present  under  conditions  which  may  be  regarded 
as  more  or  less  normal.  In  Eoy's  and  Lazarus-Barlow's* 
experiments  the  specific  gravity  of  the  tissues  was  used  as  an 
index  to  the  amount  of  tissue  fluid  present ;  a  diminution  in 
specific  gravity  being  regarded  as  indication  of  increase  of  this 
fluid.  Dr.  Oliverf  has  employed  another  method  for  arriving 
at  an  idea  of  this  quantity,  which,  in  view  of  the  importance  of 
the  point  on  which  knowledge  is  sought,  deserves  further  in- 
vestigation with  a  view  to  its  confirmation.  Oliver  showed  that, 
if  the  finger  were  einptied  of  blood  by  means  of  a  rubber  ring, 
a  drop  of  blood  obtained  from  its  tip,  immediately  after 
relaxing  the  constriction  at  the  base,  was  more  concentrated 
than  that  obtained  from  the  finger  which  had  not  been 
previously  emptied.  He  ascribed  this  difference  to  the  fact 
that  in  the  process  of  emptying,  not  only  is  the  blood  driven 
out  of  the  capillaries,  but  there  is  also  a  squeezing  of  the 
tissue  fluid  out  of  the  intercellular  spaces.  He  regards 
blood  obtained  in  the  normal  fashion  as  blood  _2)Z?t.s 
tissue  fluid.  On  comparing  this  blood  with  that  obtained 
from  the  emptied  finger,  he  finds  a  difference  which  he  takes 
to  be  a  measure  of  the  tissue  fluid  present  in  the  finger. 

The  tissue  spaces  are  separated  from  both  blood  vessels  and 
lymphatics  by  means  of  endothelium.  The  situation  of  the 
valves  in  the  lymphatic  trunks  determines  that  any  flow  of 
fluid  in  these  trunks  must  be  from  periphery  towards  centre, 
i.e.,  towards  the  great  veins  at  the  root  of  the  neck.     The 

*  W.    S.    Lazarus-Barlow,    "The    Pathology   of    the   Oedema   which 
accompanies  Passive  Congestion."     Phil.  Trans.,  p.  779,  B,  1894. 
t  Proc.  Roij.  Soc,  June  11,  1903. 


64  THE    FLUIDS    OF    THE    BODY 

lymphatic  radicles  form  a  closed  system,  so  that  fluid  only 
slowly  escapes  from  the  tissue  spaces  into  them.  Thus  coloured 
fluid  injected  into  the  tissues  passes  with  extreme  slowness  into 
the  lymphatics,  unless  the  seat  of  injectioti  be  kneaded.  Any 
movement  causing  stretching  of  aponeuroses  or  skin,  by 
increasing  the  pressure  in  the  subjacent  tissues,  will  empty  the 
tissue  spaces  into  the  lymphatics.  The  fluid  lost  in  this  way 
must  be  replenished  at  the  expense  of  the  blood.  This  is 
continually  being  renewed  in  every  part  of  the  body,  and 
therefore  bringing  up  new  fluid  to  the  tissues  to  replace  that 
lost  by  way  of  the  lymphatics. 

Most  of  our  opinions  as  to  the  factors  which  determine  the 
production  of  tissue  fluid  are  derived  from  the  study,  not 
of  the  fluid  itself,  but  of  the  lymph  flow  from  the  tissue.  It 
is  evident  that  considerable  reserve  must  be  exercised  in 
drawing  conclusions  as  to  the  amount  and  composition  of  the 
fluid  passing  from  the  blood  vessels  into  the  tissue  spaces, 
from  experiments  carried  out  on  the  composition  and  amount 
of  the  lymph  flowing  away  in  the  lymph  channels.  More 
especially  is  this  the  case  since,  as  we  shall  see,  fluid  as 
well  as  substances  in  solution  may  be  taken  away  from  the 
tissues,  not  only  by  the  lymphatics,  but  also  by  the  blood 
vessels  themselves.  Hence  the  fluid  obtained  from  a  cannula 
in  the  lymphatic  trunks  represents  only  that  portion  of  the 
transuded  fluid  which  has  escaped  reabsorption  by  the  blood 
vessels.  Its  composition  will  approach  that  of  the  transuded 
fluid  more  nearly  the  greater  the  rate  at  which  this  is  pro- 
duced, but  in  every  case  will  be  modified  in  consequence  of 
the  metabolic  exchanges  occurring  between  the  fluid  and  the 
cells  it  bathes. 

If  however  we  bear  these  limitations  in  mind,  we  may,  by 
study  of  the  lymph-flow  from  a  part  of  the  body,  arrive 
at  some  approximate  idea   of  the  factors  involved  in   the 


EXCHANGE    OE    FLUIDS  IN  THE    BODY PRODtJCTION    OF    LYMPH      65 

production  of  tissue  fluid  from  the  blood  vessels.  Here,  as  in 
all  similar  investigations,  we  have  to  measure  accurately  the 
physical  forces  concerned  and  the  energies  which  are  available 
for  the  production  of  the  fluid,  before  we  can  come  to  a  con- 
clusion as  to  the  part  played  by  the  cells  of  the  blood  vessels 
and  tissues  in  the  process.  What  are  these  factors  ?  The 
production  of  tissue  fluid  is  limited  to  the "  region  of  the 
capillaries  and  small  veins.  Through  these  blood  is  flowing 
at  a  pressure  varying  in  different  localities  and  according 
to  the  position  of  the  body.  With  the  body  in  a  horizontal 
position  the  average  capillary  pressure  may  be  taken  as 
something  between  20  and  30  mm.  Hg.  In  the  upright 
I)osition  this  figure  may  be  considerably  increased  by  the 
addition  of  the  hydrostatic  pressure  due  to  the  column  of 
blood  between  the  heart  and  the  lower  portions  of  the  body. 
In  the  capillaries  of  the  liver  the  pressure  will  be  lower, 
probably  about  10  mm.  Hg. 

The  endothelial  wall  of  the  capillaries  presents  a  structure 
which  would  suggest  the  possibility  of  a  leakage  or  filtration. 
The  separate  flat  cells  of  which  it  is  composed  abut  on  the 
adjacent  cells,  but  are  not  directly  continuous  with  these, 
a  slender  crack  being  left  containing  either  lymph  or 
cement  substance,  probably  the  former,  which  stains  black 
with  nitrate  of  silver.  The  cells  themselves  are  not  indefi- 
nitely extensible,  so  that  distension  of  the  vessels  causes 
a  widening  of  the  intercellular  cracks  as  shown  by  the  coarse 
lines  presented  by  a  silver-stained  specimen. 

It  is  very  difiicult  to  determine  whether  the  cells  themselves 
permit  the  passage  of  the  fluid  constituents  of  the  blood,  as 
we  have  seen  to  be  the  case  in  the  intestine;  but  that  the 
cracks  between  the  cells  will  allow  of  the  passage  of  fluid  is 
suggested  by  the  fact  that  under  abnormal  conditions  white 
•  and  red  corpuscles  may  pass  out  by  these  channels.     Assuming 

F.B.  ^ 


66  THE    FLUIDS    OF    THE    BODY 

that  the  vessel  wall  is  passive  in  the  production  of  tissue 
fluid,  we  should  have  to  regard  it  as  a  more  or  less  perfect 
colloidal  membrane,  and  the  conditions  of  transudation  would  be 
given  to  us  by  a  study  of  the  behaviour  of  colloidal  membranes 
of  various  degrees  of  density,  or  permeability.  A  comparative 
study  of  such  membranes  has  been  recently  made  byBechhold.* 
It  was  shown  many  years  ago  by  Graham  that  colloidal  mem- 
branes were  impermeable  for  dissolved  colloids.  Bechhold 
shows  that  this  impermeability  is  relative.  Thus,  a  membrane 
impregnated  with  3  per  cent,  gelatin  might  allow  haemo- 
globin to  pass  through  but  would  keep  back  serum  albumin 
and  serum  globuHn ;  on  increasing  the  concentration  to  4  per 
cent,  haemoglobin  might  be  retained  but  albumoses  and 
dextrines  would  still  pass. 

This  impermeability  of  colloid  membranes  may  be  used,  as 
was  shown  by  Martin, f  to  separate  the  saline  and  fluid  consti- 
tuents from  colloid  solutions  such  as  serum.  For  this  purpose 
a  gelatin  membrane  is  deposited  in  the  meshes  of  a  Chamber- 
land  filter,  and  in  order  to  obtain  an  appreciable  amount  of 
filtrate  in  a  given  time  very  high  pressures  are  used,  i.e.,  30  to 
40  atmospheres.  Such  high  pressures  are  however  only 
necessitated  by  the  great  resistance  offered  to  the  passage  of 
fluid  through  these  thick  membranes.  When  a  thin  mem- 
brane is  employed,  such  as  a  film  of  gelatin  deposited  on 
a  piece  of  peritoneum, ^a  separation  of  water  and  salts  from 
the  serum  appears  at  a  pressure  below  40  mm.  Hg.  As  we 
have  already  seen,  there  is  a  limiting  pressure  below  which 
no  filtration  takes  place,  any  filtrate  being  reabsorbed  by  the 
colloid  solution.  This  limiting  pressure,  which  in  serum 
amounts  to  about  30  mm.  Hg.,  I  regard  as  equivalent  to  the 
osmotic  pressure   or  '  Quellungsdruck '  of  the  proteins  of  the 

*  Zeitsch.  f.  physikal  Chem.,  LX.,  p.  257,  1907. 
t  Journ.  of  Physiol,  XX.,  364,  1896. 


EXCHANGE  OF  FLUIDS  IN  THE  BODY PRODUCTION  OF  LYMPH   67 

serum,  or  rather  of  those  constituents  of  the  serum  to  which 
the  gelatin  memhrane  is  impermeable. 

If  therefore  the  capillary  wall  were  equivalent  to  a  mem- 
brane of  10  per  cent,  gelatin,  it  would  allow  the  passage  of  a 
protein-free  transudate  containing  all  the  water  and  salts  of 
the  blood-plasma,  so  long  as  the  pressure  of  the  capillaries 
exceeded  30  mm.  Hg. ;  whereas  if  the  pressure  fell  below  this 
figure,  any  protein-free  transudate  present  in  the  tissue  spaces 
would  be  reabsorbed  into  the  blood  vessels.  If  the  membrane, 
like  a  2  per  cent,  gelatin  solution,  were  partially  permeable 
to  proteins,  the  ell'ect  would  be  to  lower  the  difference  of  pres- 
sure necessary  to  give  transudation,  i.e.,  we  might  have  tran- 
sudation at  a  pressure  of  10  to  20  mm.  Hg.  The  transudate 
would  then  contain  protein,  and  the  percentage  of  protein  in 
the  transudate  would  approach  nearer  and  nearer  to  that  of 
the  circulating  plasma  the  more  permeable  were  the  vessel- 
wall. 

Pressure  differences  would  not  be  the  only  factor  deter- 
mining the  transference  of  water  and  dissolved  substances 
through  the  capillary  wall.  We  have  reason  to  believe  that 
the  capillary  wall  is  permeable  to,  i.e.,  allows  of  the  diffusion 
of  practically  all  crystalloids,  though  the  ease  with  which  the 
various  salts  will  pass  differs  according  to  the  nature  of  the 
salt.  Sodium  chloride,  for  instance,  escapes  through  or 
between  the  endothelial  cells  with  greater  rapidity  than  sodium 
sulphate.  The  capillary  wall  resembles  in  this  respect  the 
epithelial  lining  of  the  intestine. 

Any  sudden  formation  of  soluble  substances  outside  the 
vessels  will  tend,  by  raising  the  molecular  concentration  of  the 
tissue  fluid,  to  draw  water  from  the  blood,  and  therefore  to 
add  to  the  state  of  distension  of  the  tissue  spaces.  On  the 
other  hand,  an  increased  molecular  concentration  of  the  blood, 
such  as  may  be  produced  by  the  injection  of  concentrated 

F   2 


68  THE    FLUIDS    OF    THE    BODY 

solutions  of  dextrose  or  sodium  sulphate  into  the  circulation, 
will  draw  water  from  the  tissue  spaces,  and  these  in  turn  will 
draw  water  from  the  cells  of  the  tissues.  The  effect  however 
will  not  be  permanent,  since  the  dissolved  substance  present 
in  excess,  either  outside  or  inside  the  vessels,  will  gradually 
diffuse  through  the  vessel- wall  so  that  the  molecular  concen- 
tration on  both  sides  will  be  equalised.  The  greater  the 
resistance  offered  by  the  vessel-wall  to  the  diffusion  of  the 
salt,  or  crystalloid,  the  greater  will  be  the  effect  as  judged  by 
transference  of  fluid.  Sodium  sulphate,  for  instance,  which 
passes  with  difficulty  through  the  capillary  wall,  will  cause  a 
greater  degree  of  hydrsemic  plethora  than  an  equivalent  solution 
of  sodium  chloride. 

In  investigating  the  factors  concerned  in  the  production  of 
tissue  fluid  and  lymph,  our  first  care  must  be  to  see  how 
far  the  pressure  differences  existing  between  the  blood 
and  the  tissue  spaces  are  responsible  for  the  passage  of 
fluid  into  these  spaces.  We  must  then  enquire  into  the  part 
played  by  the  differences  of  concentration,  and  finally  see 
whether  any  effects  remain,  which  are  inexplicable  as  results 
of  hydrostatic  pressure  or  osmotic  differences  and  must  there- 
fore be  referred  to  an  active  intervention  on  the  part  of  the 
endothelial  cells  themselves. 

(1)  The  Part  Played  by  Pressure  Differences. — Much  con- 
fusion has  crept  into  the  interpretation  of  the  experiments  on 
lymph  formation  by  neglecting  to  give  due  importance  to  the 
great  differences  which  exist  between  the  conditions  of  lymph 
formation  in  various  parts  of  the  body.  According  to  Ludwig's 
filtration  hypothesis,  the  amount  of  tissue  fluid  formed  in  any 
part  should  be  proportional  to  the  difference  between  the 
intracapillary  blood  pressure  and  the  pressure  ruling  in  the 
extracapillary  spaces.  Where  there  is  normally  a  consider- 
able production  of  tissue  fluid  and  an  easy  access  for  this  fluid 


EXCHANGE  OF  FLUIDS  IN  THE  BODY PRODUCTION  OF  LYMPH   69 

into  the  lymphatics  we  should  expect  to  find,  if  the  hypothesis 
be  correct,  that  the  lymph  flow  also  varies  with  this  difference 
of  pressures.  This  condition  is  found  in  the  abdominal  organs. 
The  fact  that  all  the  lymphatics  of  the  body,  with  the  excep- 
tion of  those  on  the  upper  part  of  the  chest,  finally  pour  their 
contents  into  the  thoracic  duct,  has  led  many  to  doubt  the 
possibility  of  drawing  conclusions  as  to  lymph  production 
by  observations  carried  out  on  the  lymph  flow  through  this 
duct.  It  is  easy  to  assure  oneself  that  this  objection  is 
without  weight,  since  under  normal  circumstances  the  lymph 
flow  from  practically  all  parts  of  the  body,  except  the 
abdominal  viscera,  is  so  small  that  the  part  it  contributes  to 
the  thoracic  duct  lymph  may  be  neglected. 

By  a  process  of  exclusion  we  can  show  that  the  only  organs 
which  contribute  an  appreciable  quantity  of  lymph  to  the 
thoracic  duct  are — 

(a)  the  alimentary  canal ; 

(b)  the  liver ; 

the  thoracic  organs,  the  limbs,  and  the  kidneys  being  practi- 
cally negligible  so  long  as  active  movements  are  not  being 
carried  out.  It  is  not  possible  to  exclude  the  intestinal  lymph 
from  the  thoracic  duct,  but  it  is  quite  easy,  by  ligaturing  the 
lymphatics  in  the  portal  fissure,  to  shut  off  the  lymph 
produced  in  the  liver,  and  so  to  obtain  only  that  flowing 
from  the  alimentary  canal. 

In  both  these  organs  we  can  alter  the  pressure  difference 
between  the  blood  and  tissue  spaces  by  altering  the  pressure 
in  the  blood  capillaries.  It  is  found  that  every  procedure 
which  raises  the  pressure  in  these  capillaries  increases  also 
the  lymph  flow  from  the  part  affected. 

The  lymph  flow  from  the  thoracic  duct  varies  considerably 
from  animal  to  animal,  and  may  amount  in  ten  minutes  to  any- 
thing between  1  cc.  and  10  cc.    Ligature  of  the  liver  lymphatics 


70  THE    FLUIDS    OP    THE    BODY 

causes  as  a  rule  a  diminution  of  the  flow,  perhaps  by  one- 
half,  the  solid  constituents  of  the  lymph  being  at  the  same 
time  diminished.  If  the  portal  vein  be  ligatured,  a  very  large 
rise  of  pressure  is  immediately  produced  in  the  capillaries  of 
the  intestinal  area,  and  this  rise  of  pressure  is  associated  with 
a  considerable  increase  in  the  amount  of  lymph  flowing  from  the 
duct.  On  obstructing  the  inferior  vena  cava  above  the  dia- 
phragm there  is  a  great  rise  of  pressure  in  the  vessels  of  the 
liver,  but  with  a  coincident  fall  of  arterial  pressure  :  the 
intestines  become  blanched  while  the  liver  swells.  This  rise 
of  pressure  in  the  hepatic  capillaries  is  associated  with  a  large 
increase  in  the  lymph  flow  from  the  thoracic  duct,  an  increase 
which  is  absent  if  the  liver  lymphatics  have  been  previously 
ligatured. 

The  area  of  increased  lymph  production  is  therefore  limited 
to  the  area  where  the  intracapillary  pressure  is  raised.  The 
different  sources  of  the  lymph  obtained  in  these  experi- 
ments is  also  shown  by  the  difference  in  its  composition, 
the  lymph  derived  from  the  liver  being  more  concentrated 
than  that  derived  from  the  intestines.  Liver-lymph  in  fact 
contains  nearly  as  much  protein  as  does  the  circulating  blood- 
plasma.  These  experiments  show  that  there  are  marked 
differences  between  the  intestine  and  the  liver  in  the 
mechanical  resistance  to  filtration  of  the  fluid  constituents 
of  the  plasma.  Normally  the  pressure  in  the  intestinal 
capillaries  may  be  taken  as  between  20  and  30  mm.  Hg. ;  in 
the  liver  capillaries  between  5  and  10  mm.  Hg.  On  ligature  of 
the  portal  vein,  the  pressure  in  the  intestinal  capillaries 
probably  rises  to  between  60  and  80  mm.  On  obstruction  of 
the  hepatic  veins,  the  pressure  in  the  capillaries  of  the  liver 
rises  to  about  4.0  mm.  Hg.,  and  the  pressure  in  the  intestinal 
vessels  cannot  be  below  this  level.  Yet  the  lymph-flow  from 
these  two  organs  during  rest  can  be  regarded  as  approximately 


EXCHANGE  OF  FLUIDS  IN  THE  BODY PRODUCTION  OF  LYMPH   71 

equal,  though  the  pressures  are  so  different ;  and  the  lymph- 
fiow  from  the  liver  under  a  pressure  of  30  to  40  mm.  Hg.  may 
be  two  or  three  times  as  large  as  the  lymph-flow  from  the 
intestines  with  a  capillary  blood  pressure  between  70  and 
80  mm.  Hg. 

That  the  greater  ease  with  which  fluid  escapes  from  the 
blood  in  the  liver  is  connected  with  the  permeability  of  the 
filtering  membrane  is  shown  by  the  difference  in  the  protein 
concentration  of  the  two  sets  of  lymph.  A  coarse  meshed 
filter  allows  not  only  easy  filtration  but  the  passage  of  all  the 
protein  constituents  of  the  filtering  fluid,  while  a  fine  meshed 
filter  keeps  back  a  certain  percentage  of  the  proteins  and 
requires  a  higher  pressure  in  order  that  filtration  should  take 
place  at  all. 

Again,  if  the  descending  thoracic  aorta  be  obstructed,  the 
pressure  in  the  intestinal  capillaries  must  fall  to  between  10 
to  20  mm.  Hg.,  and  the  same  pressure  will  be  found  in  the 
hepatic  cajoillaries,  i.e.,  there  is  a  great  fall  in  the  normal 
pressure  of  the  intestinal  capillaries,  but  no  appreciable  fall 
in  the  hepatic  capillary  pressure.  The  lymph  flow  from 
the  thoracic  duct  under  these  circumstances  is  generally 
diminished,  but  not  abolished,  and  the  lymph  at  the  same  time 
becomes  more  concentrated.  If  however  the  liver  lymphatics 
be  previously  ligatured,  obstruction  of  the  thoracic  aorta 
entirely  stops  the  flow  from  the  thoracic  duct,  showing  that 
previously  the  whole  of  the  lymph  had  been  derived  from  the 
liver,  viz.,  from  the  region  where  the  intracapillary  pressure 
was  not  appreciably  altered.  The  wall  of  each  capillary 
seems  to  be  constructed  to  resist  a  certain  pressure. 
Variations  in  this  pressure  will  affect  the  amount  of  transuda- 
tion without  reference  to  what  may  happen  to  be  the  absolute 
height  of  the  pressure  attained. 

When  we  come  to  deal  with  the  production  of  tissue  fluid  in 


72  THE    FLUIDS    OF    THE    BODY 

the  limbs  and  subcutaneous  tissues,  the  enquiry  becomes  more 
comjDlex  and  the  results  more  difficult  to  interpret,  owing  to 
the  fact  that  in  the  resting  limb  there  is  no  flow  from  the 
tissue  spaces  at  all.  This  absence  of  flow  may  be  ascribed 
either  to  relative  impermeability  of  the  capillary  wall  itself, 
or  to  an  increased  resistance  presented  to  the  passage  of  fluid 
from  the  tissue  spaces  into  the  lymphatic  capillaries.  That 
some  part,  at  any  rate,  is  played  by  the  latter  factor  is 
indicated  by  the  fact  that  if  a  coloured  fluid,  such  as  solution 
of  Berlin  blue,  be  injected  under  the  skin,  it  finds  its  way 
into  the  lymphatics  wdth  extreme  slowness,  unless  its  absorption 
is  facilitated  by  kneading  the  limb  or  by  carrying  out  passive 
movements.  Ludwig  has  shown  that  the  lymphatics  of  the 
aponeuroses  are  so  arranged  that  every  movement,  active 
or  passive,  tends  to  pump  fluid  from  the  tissue  spaces  into 
the  lymphatics,  and  from  the  smaller  into  the  larger  lymph 
trunks.  Experiments  on  the  j)roduction  of  lymph  in  the 
limbs  have  therefore  always  to  be  associated  with  kneading 
or  passive  movements  in  order  to  get  any  flow  of  lymph 
at  all.  Experimenting  in  this  way,  we  find  that  alterations 
of  the  pressure  in  the  capillaries  of  the  limb  effect  changes 
in  the  lymph  flow  which  are  insignificant  as  compared 
with  those  observed  under  similar  conditions  in  the  abdominal 
organs.  Obstruction  of  a  large  venous  trunk  has,  in  most 
experiments,  been  attended  with  a  trifling  increase  of 
lymph  production,  but  arterial  hypersemia  has  often  had 
little  or  no  effect,  and  many  authorities,  among  them 
Heidenhain,  have  concluded  that  there  is  no  appreciable 
connection  between  the  intracapillary  pressure  and  the  pro- 
duction of  tissue  fluid. 

The  results  however  may  be  very  different  if,  instead  of 
measuring  the  lymphatic  outflow  from  the  limb,  we  determine 
the  amount  of  tissue  lymph  contained  in  its  meshes  by  one  of 


EXCHANGE    OF    FLUIDS  IN  THE    BODY PRODUCTION    OF    LYMPH       73 

the  methods  which  I  mentioned  earher  in  this  lecture.  Thus 
although  Lazarus  Barlow  was  unable  to  detect  any  noticeable 
difference  in  the  specific  gravity  of  muscle  as  a  result  of  moderate 
venous  congestion,*  he  found  that  any  relative  increase  in  the 
circulation  of  blood  through  a  limb  (as  would  be  caused  by  the 
application  of  Esmarch  bandages  to  the  other  limbs)  caused  a 
fall  in  the  specific  gravity  of  the  muscle  and  a  rise  in  the 
specific  gravity  of  the  blood,  f  These  changes  he  interpreted 
as  indicating  an  increased  transudation  of  tissue  fluid. 

According  to  Oliver  a  similar  parallelism  is  found  between  the 
amount  of  tissue  lymph  in  the  finger  and  the  general  blood 
pressure.  I  reproduce  here  some  curves  (Figs.  3  and  4,  p. 
74)  in  which  this  connection  between  the  amount  of  tissue 
lymph  and  blood  pressure  in  man  is  graphically  represented. 
We  may  conclude  that  whereas  in  the  limb  the  turgescence  of 
the  tissues,  i.e.,  the  distension  of  their  spaces,  is  probably 
closely  connected  with  the  intracapillary  pressure,  the  increase 
of  tissue  fluid  produced  by  a  rise  of  pressure  does  not  normally 
attain  such  an  extent  as  to  cause  an  overflow  into  the 
lymphatics  and  therefore  a  marked  parallelism  between  the 
lymph  flow  and  the  capillary  blood  pressure.  We  shall  have 
occasion  to  return  to  this  point  later  on  when  dealing  with 
the  factors  which  determine  the  production  of  dropsy. 

We  may  here  note  simply  that  it  is  possible,  by  altering  the 
nutritional  conditions  of  the  tissues,  to  bring  about  a  condition 
of  affairs  in  the  limb  very  closely  analogous  to  that  found  to 
exist  in  the  abdominal  organs.  If  a  limb  be  scalded  so  as  to 
induce  a  state  of  inflammation,  the  lymph  flow  from  the 
limb  is  largely  increased,  the  lymph  becomes  richer  in  proteins, 
and  its  amount  varies  regularly  and  in  proportion  to  the 
capillary  blood  pressure. 

-  Fhil.  Trans.,  B,  1894,  p.  779. 

t  Journ.  of  Physiol,  Proceedings,  Vol.  XVI.,  13,  1894. 


74 


THE    FLUIDS    OF    THE    BODY 


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Fig.  3.  Blood  pressure  in  man,  taken  by  Oliver's  method  in  the  radial 
arterj^  to  show  variations  in  blood  pressure  induced  by  the  ingestion  of 
food. 

Fig.  4.  Percentage  of  corpuscles  (o,000,()()()  per  cb.  mm.  =  100)  in 
blood  from  finger  at  different  times  after  takiug  a  meal.  The  difference 
between  the  two  curves  gives  a  measure,  according  to  Oliver,  of  the 
amount  of  tissue  lymph  present  in  the  tissue  spaces  of  the  finger  (Oliver). 


EXCHANGE    OF    FLUIDS  IN  THE    BODY PRODUCTION    OF    LYMPH       75 

The  close  connection  between  capillary  blood  pressure  and 
transudation  of  fluid  into  the  tissue  spaces  is  shown  when  we 
alter  the  total  amount  of  the  circulating  blood.  An  increase 
in  volume  of  the  circulating  blood  is  accommodated  by  a 
dilatation  of  the  arterioles,  especially  in  the  splanchnic  area, 
and  by  a  dilatation  of  the  veins.  The  arterial  pressure  is 
unaltered  or  slightly  increased ;  but  there  is  a  considerable 
relative  rise  of  pressure  in  the  veins  near  the  heart  as  well  as 
in  the  portal  vein.  The  velocity  of  blood  flow  through  the 
dilated  vessels  may  be  increased  two-  or  three-fold  so  that 
there  is  a  rise  of  pressure  in  all  the  capillaries  of  the  body. 
The  efl'ect  of  this  rise  on  lymph  production  is  best  marked  in 
the  abdominal  organs.  In  the  limbs  we  shall  have  increased 
turgescence,  i.e.,  filling  of  the  tissue  spaces,  but  no  great 
increase  in  the  lymph  flow.  From  the  liver  and  intestines 
the  lymph  flow  may  be  very  largely  increased,  and  this 
increase  results  in  a  concentration  of  the  blood  as  well  as  of 
the  plasma,  since  it  involves  the  escape  of  a  fluid  from  the 
vessels  which  is  less  concentrated  than  the  circulating  plasma. 
The  same  efl'ect  is  seen  if  we  produce  a  relative  plethora,  not 
by  injection  of  defibrinated  blood,  but  by  causing  universal 
constriction  of  the  blood  vessels,  as,  e.g.,  by  injection  of 
adrenalin.  It  is  suflicient  to  raise  the  blood  pressure  by 
50  mm.  Hg.  for  the  period  of  a  few  minutes  to  increase  the 
concentration  of  the  blood  by  10  or  15  per  cent. 

These  experiments  show  us  not  only  that  the  production 
of  tissue  lymph  is  dependent  on  the  difterence  between  the 
pressures  inside  and  outside  the  vessels,  but  also  that  the  per- 
meability of  the  vessel-walls  themselves  exercises  an  important 
influence  on  the  process,  so  that  filtration  as  a  factor  in  lymph 
production  is  best  marked  in  those  parts  of  the  body,  such  as 
the  liver,  where  the  resistance  of  the  wall  of  the  blood  vessels  is 
only  just  sufficient  to  keej)  back  the  formed  elements  of  the  blood. 


76  THE    FLUIDS    OF    THE    BODY 

The  formation  of  tissue  fluid  will  be  affected  also  by  chemical 
conditions,  i.e.,  by  the  chemical  character  of  the  circulating 
fluid  or  of  the  fluid  in  the  surrounding  tissue  spaces.  Let  us 
examine  first  the  influence  of  changes  in  the  composition  of  the 
blood.  The  chief  resistance  to  the  escape  of  plasma  through  the 
cracks  between  the  endothelial  cells  is  afforded  by  the  presence 
of  proteins  dissolved  in  this  fluid.  The  less  the  protein  con- 
tained in  the  plasma,  the  more  easily  will  it  filter  through  any 
membrane,  and  the  more  easily  will  a  filtrate  free  from  protein 
be  separated  from  it  by  filtration  through  a  colloid  membrane. 

It  is  not  surprising  therefore  to  find  that  a  reduction  of  the 
protein  content  of  the  plasma  is  associated  with  an  increased 
production  of  lymph,  and  with  a  greater  susceptibility  of  the 
lymph  production  to  changes  in  capillary  pressure.  If 
hydrsemic  plethora  be  induced  by  large  injections  of  salt 
solution  into  the  blood  vessels,  a  very  rapid  lymph  flow,  as 
much  as  10  to  20  cc.  per  minute,  may  be  observed  from  the 
thoracic  duct.  In  the  production  of  this  fluid  however,  the 
co-operation  of  two  factors  is  involved,  viz.,  altered  composi- 
tion of  the  blood,  and  a  rise  of  capillary  pressure  in  all  the 
abdominal  viscera.  The  latter  can  be  avoided  by  drawing  off 
from  the  animal  an  amount  of  blood  equal  to  that  of  the 
normal  saline  fluid  injected.  When  a  pure  hydraemia  is 
produced  in  this  way,  the  lymph  flow  is  increased,  but  only 
to  an  amount  about  twice  as  great  as  that  obtained  from  the 
same  animal  before  the  hydraemia  was  produced. 

Closely  connected  with  the  increased  lymph-flow  obtained 
in  conditions  of  hydrgemic  plethora  is  that  observed  after 
the  injection  of  a  strong  solution  of  crystalloids,  such  as 
sugar,  sodium  chloride,  or  sodium  sulphate,  bodies  which  were 
included  by  Heidenhain  in  his  second  class  of  lymphagogues. 

If,  for  example,  30  cc.  of  a  30  per  cent,  solution  of  dextrose 
be  injected  into  the  jugular  vein  of  an  animal,  the  immediate 


EXCHANGE  OF  FLUIDS  IN  THE  BODY PRODUCTION  OF  LYMPH   77 

effect  is  to  raise  the  molecular  concentration  of  the  circulating 
blood,  and  therefore  its  osmotic  pressure.  The  capillary  wall, 
like  all  other  animal  membranes,  permits  of  the  passage  of 
water  with  the  greatest  ease.  Water  therefore  passes  from 
the  tissue  spaces  into  the  blood,  and  the  molecular  concentra- 
tion rises  in  the  tissue  spaces.  This  in  its  turn  induces  a 
passage  of  water  from  the  tissue  cells  into  the  spaces.  The 
final  result  is  increased  molecular  concentration  of  all  the 
constituents  of  the  body  and  a  change  in  the  spatial  distri- 
bution of  the  water,  the  cells  being  shrunken  and  the  tissue 
and  blood  fluids  increased.  As  a  result  of  the  increased 
volume  of  circulating  blood,  a  condition  is  produced  analogous 
to  that  which  can  be  brought  about  by  the  injection  of 
normal  salt  solution  into  the  circulation,  viz.,  an  hydraemic 
plethora. 

As  in  this  latter  condition  the  increased  bulk  of  circulating 
fluid  causes  an  alteration  in  its  distribution,  the  normal 
arterial  pressure  can  only  be  maintained  by  opening  what 
Foster  calls  the  "  splanchnic  flood  gates  "  and  thus  allowing 
the  surplus  blood  to  distend  the  capillaries  and  big  veins  in 
the  abdomen  and  in  the  neighbourhood  of  the  heart. 

A  stud}^  of  the  pressures  in  the  different  parts  of  the 
vascular  system  shows  that  the  results  are  the  same  whether 
the  hydremic  plethora  be  induced  by  the  injection  of  large 
quantities  of  normal  salt  solution,  or  by  the  injection  of  small 
quantities  of  concentrated  salt  solution.  In  the  latter  case 
however,  increased  fluid  is  derived  from  the  cells,  and  a 
plethysmograph  record  shows  that  all  parts  of  the  body,  except 
the  abdominal  organs  themselves,  shrink.  If  we  place  a  limb 
and  an  abdominal  organ — whether  kidney,  intestine  or  liver — 
into  plethysmographs,  we  And  that  injection  of  hypertonic 
solution  causes  an  almost  instantaneous  shrinking  of  the  limb 
associated  with  an  increased  volume  of  the  abdominal  organ. 


78 


THE    FLUIDS    OF    THE    BODY 


As  in  hydraemic  plethora  these  changes  in  blood  pressure 
and  blood  constituents  cause  a  very  largely  increased 
production  of  lymph  in  the  abdominal  organs,  and  a  great 
increase  in  the  lymph  flow  from  the  thoracic  duct.  That 
the  mechanical  changes  induced  by  injection  of  strong  salt 
solution  are  mainly  responsible  for  the  increased  lymph- 
flow  is  shown  by  the  fact  that,  if  we  prevent  them  by  the 
withdrawal  of  the  appropriate  quantities  of  blood,  there  is 
practically  no  increase  of  lymph.  These  facts  are  well  shown 
in  the  accompanying  curves  (Figs.  5  and  6),  which  represent 
graphically  the  results  of  the  typical  experiments,  of  which 
the  chief  data  may  be  here  quoted. 


A.   Effect  of  Injection  of  Ce,ystalloids  on  the  Blood  Pressube. 

Bitch.  8  kilos. 

Time.  Fem.  art.  Portal  vein.  Inf.  cava. 

11.15         .  .  100  mm.  Hg.       80  mm.  UgSO^       12  mm.  MgS04 

i  40  grms.  dextrose  in  water  (50  cc.  fluid)  iniected 
11.20       )       ^  V  ;      J 


11.20 

65 

210 

180 

11.30 

105 

147 

50 

11.40 

120 

120 

25 

11.50 

118 

120 

17 

12.0 

114 

124 

18 

12.15 

107 

126 

18 

Effect  of  Injection  of  Crystalloids  on  Lymph-flow. 
Dog.     12  kilos.     Kidney  vessels  ligatured. 


Lymph  in  10  mins. 

3  cc. 

3-6 

30 

grms. 

dextrose  in  30 

33 

31 

20 

12 
9 

8-4 
6-4 

cc. 

water 

injected 

into 

jugular 

vein 

EXCHANGE  OF  FLUIDS  IN  THE  BODY PRODUCTION  OF  LYMPH   79 


i~i~rr'^"'n~;~rr"rTi^7  i  i  i  i  i  '  "i~t  '^      T 


5-af:^ 


t-4-+-f-rf-,!-i-i-+j-T^n  ;  rtilll~r^Lt:n  L.-T 

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,    -|-+-♦ili^^-^-^-+^-i-^-r-t+^-^-^-+^-+^■i-r-^-l■-|-,-|-^r^t^""'~f^^"l  i  1  i   I  i  i  '  i   '  i   i  i  i   I   ' 


r-, i_?!?T-i   4-  -4— I— 1-- 

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o  I  I  I   i  I  1  I   j  I  I  jl  I  I  I  I  I  I   I  I 


-M- 


50 


60  minutes 


fn/.  of  40qram5  dextrose 


Fig. 


TTi  i   i   I   i   I   I   !   I   !    I  ' 
-T-|  I  rrT-ri-T+-i"-t~t-* 

:^i=i=i=i--=M-+4^'f+"^"-?T-|-t-t--t4- 


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I  I  I  I  I  i  I  i  I  I  ! 


■M-H+ 
t-H-4 


'eOniihutes' 


6 tea  to  240  cam      Inj.  ta grams  dextrose 


Figs.  5  and  6. — Curves  showing  the  relation  between  the  pressures  in  the 
portal  vein,  inferior  vena  cava  and  carotid  artery  and  the  lymph  flow  from 
the  thoracic  duct,  after  injection  of  a  strong  solution  of  dextrose.  In  Fig.  6 
the  rise  of  pressure  was  prevented  by  bleeding. 

In  both  curves  the  divisions  of  the  abscissa  indicate  minutes. 
Each  division  of  the  ordinates  expresses  ; 

(a)  Rate  of  flow  of  lymph  (in  c.cm.  in  10  minutes). 

(fe)  Height  of  pressure  in  femoral  artery  (in  cm.  Hg). 

(c)  Height  of  pressure  in  portal  vein  and  vena  cava  (in  centimetres  MgS04  solution). 
Each  curve  represents  two  experiments,  one  in  which  the  three  pressures  were  recorded,  and 
a  similar  one  in  which  the  lymph-flow  and  the  arterial  pressure  were  recorded.      In  each  case 
experiments  were  chosen  in  which  the  arterial  pressures  underwent  corresponding  changes. 
The  double  line  —  rate  of  lymph-flow. 
The  thick  line     =  pressure  in  femoral  artery. 
The  thin  line       =  pressure  in  jjortal  vein. 
The  dotted  line  =  pressure  in  inferior  vena  cava. 


80  THE    FLUIDS    OF    THE    BODY 

B.    Effect   of  Injection  of   Crystalloids,  after  previous 
Bleeding,  on  Blood  Pressures  and  Lymph  Flow. 

Time.  Fern.  art.  Portal  vein.  Inf.  cava. 

11.45  ..  101  mm.  Hg.     78  mm.  MgS04     30  mm.  MgSO^ 

Dog  bled  to  240  cc. 

11.50         ..  61  ..  45  ..  8 

11.55         ..  72         ..46  ..  9 

18  grms.  dextrose  injected. 

Time.  Fem.  art.  Portal  vein.  Inf.  cava. 

12.15  . .  70  mm.  Hg.  120  mm.  MgS04  18  mm.  MgSOi   - 

12.20  ..  90         ..  108  ..  17 

12.30  ..  98         ..  97  ..  14 

12.45  ..  98         ..  82  ..  22 

Dog.   10^  kilos. 

Lymph  in  10  mins. 

4-6  CO. 

3-2  cc.     Bled  to  350  cc. 

1-5 

25  grms.  dextrose  in  25  cc.  water  injected. 
3-5 

7-2 
6-8. 

A  study  of  the  comparative  amounts  of  the  injected  crystal- 
loid in  blood  and  lymph  respectively  led  Heidenhain  to  the 
conclusion  that  there  was  an  actual  secretion  of  lymph  from 
the  blood  vessels,  since,  at  any  given  time  after  the  injection, 
the  lymph  contains  a  larger  percentage  of  the  injected  crystal- 
loid than  is  to  be  found  in  .the  blood.  As  Cohnstein  pointed 
out,  this  difference  is  due  merely  to  the  fact  that  the  amount 
of  sugar  is  continually  declining  in  the  blood,  so  that  the  lymph 
obtained  from  the  thoracic  duct  at  any  moment  repre- 
sents the  fluid  which  has  transuded  from  the  blood  vessels  at 
some  unknown  time  previously,  when  the  sugar  content  of 
the  blood  was  at  a  higher  level.  At  no  time  is  the  propor- 
tion of  the  injected  crystalloid  in  the  lymph  found  to  be  higher 
than  or  even  to  attain  to  the  maximum  which  is  produced 
in  the  blood  as  the  result  of  the  injection. 


EXCHANGE  OF  FLUIDS  IN  THE  BODY PRODUCTION  OF  LYMPH   81 

From  these  various  observations  we  may  conclude  that 
the  driving  force  for  the  production  of  lymph,  or  tissue 
fluid,  is  represented  by  the  difference  between  the  pressure 
in  the  capillaries  and  the  pressure  in  the  tissue  spaces  out- 
side the  capillaries.  The  amount  actually  formed  in  any 
organ  of  the  body  under  a  given  pressure  is  conditioned  by 
the  permeability  of  the  cajpillary  wall,  and  perhaps  by  the 
ease  with  which  the  fluid  escapes  from  the  extracapillary 
spaces  into  the  lymphatics. 

We  have  seen  no  reason  to  ascribe  any  part  of   the  pro- 
cess to  the  active  intervention  of,  i.e.,  the  evolution  of  energy 
by,   the  cells    of   the  capillary  wall,   or  by  the  cells  of  the 
tissues  outside  the  capillaries.      Yet  many  physiologists  are 
still  of  opinion  that  we  are  not  justified  in  thus  excluding 
cell    activity   as    an    agent    in    the    production   of    lymph. 
Let  us  examine    some   of    the    arguments   which  have  been 
put  forward  against  the  views  which  I  have  represented.     I 
would  point  out  at  the  outset  that  we  are  not   justified  in 
assuming  an  unknown  cause  so  long  as  phenomena  can  be 
exj)lained  by  a  cause  which  is  familiar  to  us.     Nor  are  we 
justified  in  rushing  to  the  explanation  of  '  vital  activity '  as 
soon  as  phenomena  present  themselves  which  are  apparently 
irregular  in  their  incidence  and  present  difficulties  in  their 
causation.     The  one  common  feature  of  all  cell  activity  is 
adaptation,  and  we  must  show  that  any  assumed  activity  of 
the  cells,  besides  involving  expenditure  of  energy  by  the  cells, 
is  also  orderly  and  adapted.      To  call  in  vital  activity  as  a 
sort  of   irresponsible  deity  to    explain    irregularities   in  our 
experimental    results    is    an    unscientific   and   I   might    say 
cowardly  device. 

When  we  examine  the  lymph  flow  from  any  part,  we  find 
as  a  rule  that  there  are  minute  differences  in  the  proportion 
of  salts  that  it  contains  as  compared  with  the  blood-plasma, 

F.B,  G 


82  THE    FLUIDS    OF    THE    BODY 

and  that  its  total  molecular  concentration  is  somewhat  higher 
than  that  of  the  blood.*  This  is,  after  all,  what  one  would 
expect.  The  lymph  bathes  the  tissue- cells  on  its  passage 
into  the  lymphatics ;  from  these  cells  it  receives  the  diffusible 
metabolites  resulting  from  their  activity.  Many  of  these 
will  pass  by  diffusion  into  the  surrounding  blood  vessels.  A 
certain  proportion,  including  the  less  diffusible,  will  be  carried 
away  by  the  lymph  stream  and  will  raise  the  molecular 
concentration  of  this  fluid. 

This  rise  in  molecular  concentration,  which  results  in  a 
living  cell  or  tissue  as  a  result  of  normal  activity,  can  be 
easily  shown  in  the  case  of  muscle.  When  pronounced  it 
must  act  as  an  additional  driving  force  for  the  lymph,  since 
any  increase  in  the  molecular  concentration  of  the  extra- 
vascular  fluid  will  cause  an  osmotic  flow  of  water  from  the 
vessels  into  the  surrounding  spaces.  By  such  a  mechanism 
we  may  account  for  a  small  increase  in  lymph  production, 
which,  according  to  Asher  and  Bainbridge,  accompanies 
activity  in  the  submaxillary  gland,  as  well  as  for  the  more 
definite  increase  in  the  lymph  flow  from  the  liver  when  the 
activity  of  this  organ  is  excited  by  the  injection  of  bile  salts 
into  the  circulation. 

There  is  no  need  to  assume  in  this  case  that  the  tissue  cells 
exercise  some  sort  of  mystical  attraction  on  the  fluid  con- 
stituents of  the  blood-plasma.  It  is  conceivable,  though  not 
proved,  that  certain  metabolites  might  cause  more  or  less 
contraction  of  the  endothelial  cells,  so  increasing  their  per- 
meability, but  there  is  no  evidence  for  the  existence  of  such 
a  mechanism,  and  still  less  for  the  assumption  that  energy 


'-  Carlson  finds  that  the  lymj^h  flowing  from  the  cervical  lymphatic  or 
from  the  salivary  glands  may  have  a  molecular  concentration  considerably 
below  that  of  the  blood  plasma.  His  results  are  however  so  irregular, 
that  it  is  difficult  to  draw  any  conclusions  s-g  to  their  significance. 


EXCHANGE  OF  FLUIDS  IN  THE  BODY PRODUCTION  OF  LYMPH   83 

for  the  passage  of  the  fluid  from  the  blood  vessels  to  the 
tissue  spaces  is  furnished  by  the  metabolic  activity  of  the 
endothelial  cells,  i.e.,  that  these  cells  act  as  little  machines 
or  motors  for  the  production  of  lymph. 

I  must  say  I  am  unable  to  appreciate  the  stress  which 
has  been  laid  by  some  authors  on  the  fact  that  the  flow 
of  lymph  from  the  thoracic  duct  may  continue  for  some 
time  after  death.  Surely  the  fact  that  lymph  continues  to  be 
produced  in  a  dead  animal  can  hardly  be  regarded  as  an 
argument  for  the  vital  intervention  of  cells  in  the  process. 
This  j^ost  mortem  flow  of  lymph  is  best  marked  in  cases  where 
during  life  the  lymph  production  has  been  largely  increased 
as  the  result  of  the  injection  of  some  form  of  lymphagogue. 
When  the  animal  dies  by  stoppage  of  the  heart,  the  big 
veins  and  liver  capillaries  are  full  of  blood  at  a  pressure 
which  may  be  greater  than  the  normal ;  the  liver-cells  may 
contain  fluid  vacuoles  and  the  lymphatics  both  of  the  liver 
and  intestines  are  distended  with  lymph.  All  the  tissue 
spaces  of  the  abdomen  are  in  a  condition  of  turgescence.  It 
is  not  surprising  that  after  death  the  turgescence  gradually 
diminishes,  the  shrinking  of  the  distended  spaces  causing  a 
gradual  expulsion  of  the  lymph  into  the  cisterna  magna  and 
along  the  thoracic  duct,  while  the  flow,  due  to  the  simple 
emptying  out  of  the  preformed  lymph,  may,  so  long  as  the 
pressure  in  the  liver  capillaries  remains  positive,  be  aided  by 
the  continuance  of  the  process  of  transudation,  i.e.,  by  a  new 
formation  of  lymph  from  the  liver  capillaries. 

Among  the  lymphagogues  described  by  Heidenhain  are  a 
series  of  bodies  which  he  places  in  a  class  by  themselves,  all 
of  which  are  active  poisons  and  include  such  substances  as 
commercial  peptone,  leech  extract,  extract  of  crayfish,  etc. 
The  action  of  these  bodies,  as  I  showed  in  1894,  is  practically 
confined  to  the  liver.     This  is  seen  in  the  records  of  two 

G  2 


84  THE    FLUIDS    OF    THE    BODY 

experiments,  in  one  of  which  the  portal  lymphatics  \/ere 
ligatured.  Their  injection  evokes  an  increased  flow  of  lymph 
from  the  thoracic  duct,  which  is  more  concentrated  than  the 
mixed  lymph  obtained  before  the  injection  (Fig.  7).  Their 
action  has  been  variously  interpreted  as  due  to  stimulation  of 

Effect  of  Ixjectiois'  of  Decoction  of  Mussels  on  Thoracic  Duct 

Lymph. 

A.  Portal  lymphatics  free. 

Lymph  in  10  mins.  Total  solids  in  lymph. 

3-6  cc — 

3'6  cc.      . .  .  .  ....  .  .  4"93  per  cent. 

A  decoction  of  mussels  injected  into  jugular  vein. 

26  cc.         . .  . .  .  .  .  . .  o'94  per  cent. 

23  cc .  .  0-89 

21  cc — 

19-6  cc ...  . .  — 

16  cc — 

13  cc.         ..  ..  ..  ..  ..  0*38  per  cent. 

B.  Portal  lymphatics  ligatured. 
Lymph  in  10  mins. 

2-8  cc -..  ..  — 

3'2  cc.      .  .  .  .  .  .  .  .  .  .         3"53  per  cent. 

A  decoction  of  mussels  injected  into  jugular  vein. 

3  cc.         . .  . .  . .  . .  . .         3'88  per  cent. 

4  cc.         . .  . .  .  .  . .  .  .  — 

3-2  cc — 

2-8  cc.      . .  . .  . .  . .  . .         3'73  per  cent. 

the  capillary  endothelium  (Heidenhain),  or  to  stimulation  of 
the  secreting  cells  of  the  liver  (Asher).  For  neither  of  these 
views  is  there  any  sufficient  evidence.  The  lymphagogues  do 
not  produce  an  increased  flow  of  bile,  nor  does  the  lymph 
obtained  as  a  result  of  their  injection  difter  from  the  transu- 
dation produced  under  other  circumstances  in  the  liver. 
Heidenhain  based  his  view  of  their  stimulating  action  on  the 
endothelial  cells  on  the  fact  that  prolonged  ischsemia  of  the 


EXCHANGE    OP    FLUIDS  IN  THE    BODY PJaODUCTION    OF   LYMPH       85 

liver,  brought   about    by  obstruction   of   the  thoracic  aorta, 
rendered   any  subsequent   injection   of   these   lymphagogues 


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without  effect.  If  we  repeat  this  experiment  of  obstruction  of 
the  thoracic  aorta,  we  find  that,  on  admitting  blood  at  the 
end  of  an  hour's  obstruction,  there  is  a  rapid  rise  of  pressure 


86 


THE   FLUIDS    OF   THE   BoDY 


in  the  portal  vein,  pointing  to  a  considerable  obstruction  in 
the  liver  capillaries.  During  the  first  tv/enty  or  thirty  minutes 
after  the  blood  has  been  let  in,  the  lymph  flow  from  the 
thoracic  duct  is  largely  increased  and  contains  blood  corpuscles, 
pointing  to  severe  injury  of  the  capillary  walls.  Details  of 
such  an  experiment  are  given  here. 

Effect  of  Abdominal  Ischemia  on  Lymph  flow. 


Time. 

Lymph  in  10  mins. 

Lymph. 

11.0—11.10 

. .     3-6  cc.       . 

.     3-6 

cc. 

Aorta  blocked  at  11.25 

11.25—1.25 

..     1-6     „       . 

.     17 

>) 

Aorta  released  at  1.25. 

1.25—35 

..        6     „       . 

.       6 

>j 

(Bloody). 

35—45 

..        9     „       . 

9 

j> 

>> 

45 — 55 

..     9-2     „       . 

9-2 

j> 

J5 

Effect  of  Long  Continued  Ischemia  on  Blood  presstjbe  in 
Abdominal  Vessels. 

Dog.     15|  kilos.     Consecutive  readings  at  one  minute  intervals. 


Time. 


12.0  midday 


1.0  p.m. 
2.0  p.m. 


Fem.  art. 

96 
96 

12  (aorta  obstructed) 

8 


Portal  vein. 

100 

100 

51 

48 

8  ..  51 

8  ..  54 

8  ..  54 

9  ..  52 
9                     ..                     49 

75  (obstruction  relieved)    180 
74  . .  260 


Vena  cava. 

30 
30 
36 
36 
44 
44 
-  44 
42 
30 
26 
36 


It  is  not  surprising  that  a  capillary  wall,  which  has  been 
disorganised  in  this  way  by  prolonged  ansemia,  should  not 
betray  any  further  change  of  its  permeability  as  the  result  of 
an  injection  of  a  substance  which  is  normally  poisonous  for 
it.  I  agree  with  Heidenhain  that  the  lymphagogue  effect  of 
these  substances  is  due  to  a  direct  action  on  the  lining  cells 
of  the  capillary  vessels.     But  whereas  he  regards  their  action 


EXCHANGE  OF  FLUIDS  IN  THE  BODY PRODUCTION  OF  LYMPH   87 

as  that  of  a  stimulant  to  increased  activity,  I  regard  them  as 
diminishing  the  vital  properties  of  the  capillary  wall,  and 
therefore  its  resistance  to  the  transudation  of  fluid. 

In  a  subsequent  lecture  I  hope  to  show  that  the  balance  of 
forces,  which  determine  the  distribution  of  the  fluid  of  the 
body,  can  be  accounted  for  on  the  so-called  mechanical  theory 
of  lymph  formation  which  I  have  set  forth  above,  and  that 
we  get  no  aid  in  our  explanation  of  the  manifold  adaptations 
of  the  vascular  system  from  the  assumption  of  an  active 
co-operation  of  the  endothelial  or  tissue  cells  in  the  production 
of  lymph. 


LECTUEE   V 

THE    ABSORPTION    OF    THE    INTERSTITIAL    FLUIDS 

Any  diminution  of  the  total  fluid  of  the  body  must  involve, 
as  a  first  step,  the  taking  up  of  the  interstitial  fluid  into  the 
circulating  blood,  in  order  that  it  may  be  carried  to  the  organs, 
such  as  kidneys,  lungs  or  skin,  by  which  it  is  excreted. 

The  mechanism  of  this  absorption  cannot  be  regarded  at 
present  as  settled.  In  my  last  lecture  I  had  occasion  to 
speak  of  the  absorption  by  way  of  the  lymphatics,  and  there 
mentioned  the  anatomical  mechanisms  described  by  Ludwig, 
Recklinghausen,  and  their  pupils,  by  means  of  which  all  the 
muscular  movements  of  the  body,  including  those  of  respira- 
tion, were  utilised  for  the  pumping  of  fluid  from  the  tissue 
and  serous  spaces  into  the  lymphatics,  and  along  these  into 
the  blood  stream.  This  mode  of  absorption  from  most  parts 
of  the  body  must  require  considerable  time.  It  is  the  only 
way  which  is  open  to  insoluble  particles,  such  as  Indian  ink 
used  in  tattooing  or  micro-organisms,  living  or  dead,  which 
have  effected  an  entrance  into  the  tissues. 

The  question  arises  as  to  how  far  the  lymphatic  channels 
are  necessary  for  the  absorption  of  the  normal  constituents  of 
lymph.  Pathological  evidence  certainly  appears  to  indicate 
that  for  certain  of  the  normal  constituents  lymphatic  channels 
are  necessary.  We  know  that  complete  obstruction  of  these 
lymphatics,  such  as  occurs  in  elephantiasis,  causes  great 
lymphangiectasis  with  overgrowth  of  the  subcutaneous  con- 
necting tissues;  and  the  presence  of  lymphatics  throughout 
practically    all  parts    of    the    body   suggests  that   there   are 


THE    ABSOEPTION    OF    THE    INTERSTITIAL    FLUIDS  89 

constituents  of  the  lymph  which  are  incapable  of  absorption 
by  any  other  way  than  that  of  the  lymphatics.  That  the 
lymphatics  are  not  the  only  channel  of  absorption  is  shown 
by  the  results  of  numerous  experiments  which  have  been 
carried  out  on  absorption  by  the  blood  vessels. 

We  know,  for  instance,  that  strychnine  or  other  drug  injected 
under  the  skin  of  a  limb  will  exert  its  poisonous  effects  on  the 
nervous  system  long  before  the  drug  itself  appears  in  the 
lymph  flowing  from  the  limb,  and  therefore  before  it  can  have 
arrived  by  way  of  the  lymphatics  in  the  circulation.  The 
very  scanty  lymph  flow  from  a  limb  shows  moreover  that 
the  ordinary  interchanges  between  the  living  tissues  and  the 
blood  (interchanges  which  involve  oxygen  and  carbon  dioxide 
as  well  as  the  foodstuffs  and  excreta  of  the  cells),  are  carried 
out  through  the  interstitial  fluid  without  the  intermediation 
of  the  lymphatics  at  all.  Nor  is  the  mechanism  of  these 
interchanges  difficult  to  understand,  in  the  case  at  any  rate 
of  most  of  the  substances  concerned.  Our  experiments  on 
lymph  production  have  shown  that  there  is  osmotic  inter- 
change between  the  extravascular  and  the  intravascular  fluids. 
Oxygen,  carbon  dioxide,  diffusible  substances,  or  water,  will 
pass  out  of  the  capillaries  in  response  to  the  ordinary  osmotic 
differences.  Thus  we  find  a  diminishing  scale  of  oxygen 
tensions  from  red  corpuscles  to  tissue  cell,  and  a  diminishing 
scale  of  CO2  tensions  from  tissue  cell  to  blood  plasma. 
Strychnine  introduced  into  the  tissue  spaces  diffuses  readily 
through  the  capillary  wall  into  the  circulating  blood  plasma. 

A  difficulty  arises  however  in  the  case  of  the  absorption 
of  the  normal  interstitial  fluid.  We  have  evidence  that  the 
fluid  in  the  tissue  spaces  may  be  taken  up  by  the  circulating 
blood  directly,  without  intermediation  of  the  lymphatics. 
What  are  the  factors  involved  in  this  transference  ?  This 
question  may   be  investigated  either  by  the  introduction  of 


90  THE    FLUIDS    OF    THE    BODY 

fluids  into  the  serous  cavities,  or  by  examining  the  conditions 
of  absorjDtion  of  fluid  from  the  connective  tissue  spaces  of  the 
body. 

(1)  Absorption  from  the  Serous  Cavities. — The  serous  cavities 
would  seem  to  be  especially  adapted  for  investigating  the 
mechanism  of  absorption  of  various  fluids  from  the  tissue 
spaces  of  the  body.  Like  these  they  are  in  intimate  relation 
with  a  terminal  plexus  of  lymphatics,  from  which  in  many 
places  they  are  separated  merely  by  a  thin  layer  of  endo- 
thelium, although  as  Kollossow  has  shown,  there  is  probably 
nowhere  any  direct  communication  between  the  serous  spaces 
and  the  underlying  lymphatics.  The  observations  of  Eeckling- 
hausen  and  others  show  that  fluids  as  well  as  fine  particles 
can  pass  with  relative  ease  through  the  interstices  between 
these  endothelial  cells,  so  that  a  fluid,  such  as  milk,  is  rapidly 
absorbed  from  the  peritoneal  cavity  by  means  of  the  lymphatics 
of  the  diaphragm. 

This  lymphatic  absorption  is  not  however  the  only  method 
by  which  fluid  may  be  taken  up  from  the  serous  spaces.  If, 
for  instance,  a  soluble  colouring  matter,  such  as  indigo  car- 
mine,  or  methylene  blue,  be  introduced  into  the  pleural  or  peri- 
toneal cavity,  it  may  appear  in  the  urine  within  six  minutes 
after  the  moment  of  injection,  at  a  time  when  the  lymph  in  the 
thoracic  duct  is  free  from  colour,  and  there  cannot  have  been 
sufficient  time  for  any  fluid  absorbed  by  the  lymphatics  to 
have  reached  the  circulation  by  way  of  the  thoracic  duct. 
There  is  in  fact  every  facility  for  osmotic  interchange  between 
the  blood  in  the  vessels  and  the  fluid  within  the  serous  cavities. 
A  series  of  experiments  which  I  carried  out  on  the  pleural 
cavity  some  years  ago  *  show  that  absorption  of  fluid  as  well 
dissolved  substances  may  take  place  by  means  of  the  blood 

-  Starling  and  Tubby,  Joum.  of  Fhysiol,  XVL,  140,  1894. 


THE    ABSOKPTION    OF    THE    INTERSTITIAL    FLUIDS  91 

Table  I. — Hypertonic  Solutions  of  Sodium  Chloride. 


c 
6 

X 
a> 

C|-i 

O 

=! 
ft 

Injected. 

Recovered. 

Absorbed. 

Serum. 

a 
B 

P- 

0) 

O 

d 

o 

s 

o 

5 

S 

o 

Oh 

o 
< 

c3 
o 

•S 

s 

'o 

o 

o 

'6 
'B 

o 

< 

d 

S 
o 

> 

5 

s 

< 

5 

a 

a 
y 

IH 

1^ 

1 

30' 

60 

1-2 

•72 

61 

•93 

-   1 

•163 

2 

30' 

80 

>  > 

>> 

83 

•94 

-    3 

•18 

3 

2° 

60 

>> 

>> 

57 

•8 

+    3 

•264 

19 

30' 

80 

1-22 

•74 

85 

1^03 

•66 

—     5 

•10 

•60 

•68 

20 

30' 

60 

1-5 

•91 

64 

1^21 

•785 

-    4 

•13 

•61 

•72 

4 

30' 

80 

j> 

>> 

97 

1-02 

-  17 

•21 

•63 

25 

2° 

80 

>> 

>> 

95 

•88 

•61 

-  15 

•37 

•595 

•74 

5 

2° 

80 

>» 

>> 

94 

•815 

-  14 

•44 

•69 

10 

2° 

80 

>> 

>> 

90 

•84 

-  10 

•44 

•71 

Table  II. — Hypotonic  Solutions 

0-5  PER  CENT.  NaCl. 


OF  Sodium  Chloride. 
A  =  -34. 


s 

Inj 

scted. 

Recovered. 

Absorbed. 

Serum. 

fl 

T) 

. 

R 

P4 

0) 

o 

, — , 

•  i-H 

*— ' 

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»— * 

P< 

o 

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1-2  . 
o  S  c 

6 

d 

o 

CO 

CIS 

o 

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O) 

G 

u 

a> 

p 

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c 

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6 

+3 

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>• 

O 

°1 

s 

s 

a 
O 

Fracti 
volur 

Fracti 
weig" 
injec 

< 

6 

30' 

80 

•4 

44 

•72 

•316 

36 

•084 

•44 

•615 

•63 

7 

>> 

50 

•25 

34 

•69 

•234 

16 

•016 

•2 

•61 

•63 

16 

>> 

80 

•4 

48 

•71 

•339 

•53 

32 

•061 

•4 

•57 

•66 

18 

2° 

80 

•4 

56 

•635 

•355 

•57 

24 

•045 

•275 

•64 

8 

j> 

80 

•4 

40 

•75 

•3 

40 

•1 

•5 

•575 

•65 

9 

>  J 

60 

•3 

28 

•69 

•193 

32 

•107 

•53 

•o6o 

•61 

21 

i> 

80 

•4 

44 

•71 

•31 

•60 

36 

•09 

•45 

•62 

•67 

92 


THE    FLUIDS   OF   THE    BODY 


Table  III. — Isotonic  Solutions.     1  per  cent.  NaCl.    A  =  '61. 


m 

Hi 

g 
CD 

Injected. 

RecoA 

'ered. 

Absorbed. 

Serum. 

C 

-c" 

S 

,^         3 

o 

o 

o        -g 

Is 

o 

"C 

CD 

^         =* 

d 

C33 

Ct                    O) 

M 

ti-c 
O 

S         ? 

a 

Ya 

^25 

P! 

^    -:s^ 

O     . 

"^ 

^ 

PI 

•4J 

o         cl  a> 

CS 

+3 

o 

•l-H 
1 

i     1 

CD 

a 

Pi 
(D 

s 

3 

a    .2  a 

.2^ 

-D  o 

cy  ID 

P! 
CD 
O 

o 

r-J                                C4 

!-l 

o3           03  O 

rt  "P 

ft 

o 

!> 

<D 

PM 

o        < 

> 

O         fe   " 

W^ 

<1         Ph 

12' 

30' 

100     1-0 

96 

•963 

•924 

4 

•076 

•61 

17 

30' 

80       -8 

78 

•915 

•714     -595 

2 

•086 

•595    ^7 

14 

2° 

80       -8 

70 

•8 

•56 

10 

•24 

•60 

Table  IY. — Epeect  of  Sodium  Eluoeide. 


a 

CD 

a 
•c 

CD 

><1 

CD 
O 

PI 

o 

1 

pi 

Q 

Injected. 

Recovered. 

Absorbed. 

Serum. 

PI 

CD 

a 
'% 

<D 

o 
d 

d 

o 

a 

D 
O 

!> 

Per  cent.  NaCl. 
Per  cent.  NaFl. 

< 

d 
ly 

_pi 

CD 

a 

o 

Per  cent.  NaCl. 
A 

Volume  in  cc. 
Grammes  NaCl. 

<I 

-(J 

PI 

CD 
O 

U 
CD 

Ph 

13 

2° 

60 

•952     ^095 

•68 

50 

•727 

10       ^21 

•61 

•59 

22 

2° 

80 

•39       -075 

•315 

40 

•61 

40 

•585 

24 

2° 

80 

•2         -2 

•33 

42 

•66       -61 

38       -11 

•60 

•645 

11 

30' 

80 

•5         -1 

•395 

60 

•63       ^605 

20       ^022 

•60 

•60 

vessels,  and  that  in  this  absorption  there  is  no  evidence  of  an 
active  '  pumping '  action  by  the  cells  either  of  the  blood 
vessel  wall  or  of  the  serous  membrane.* 

If  a  salt  solution  with  a  raolecular  concentration  different 
to  that  of  the  blood-plasma  be  introduced  into  the  pleural 
cavity,  there  is  an  initial  passage  of  water  into  or  out  of  the 


='=  Leathes  aud  Starling,  Juarti.  of  PhysiuL,  XVIII.,  108,  1895. 


THE    ABSORPTION    OF    THE    INTERSTITIAL    FLUIDS  93 

cavity,  according  as  the  introduced  fluid  is  hyper-  or  hypo- 
tonic to  the  blood-plasma.  When  isotonicity  has  been 
obtained  by  this  means,  the  further  interchange  is  chiefly 
concerned  with  an  equalisation  of  the  quantities  of  salts  on 
the  two  sides  of  the  absorbing  membrane ;  but  there  is  at  the 
same  time  a  slow  absorption  of  the  isotonic  fluid  from  the 
pleura,  about  5  cc.  per  hour,  which  can  be  ascribed  partly  to 
tbe  lymphatics  and  partly  to  the  colloid  concentration  of  the 
blood,  as  we  shall  see  shortly. 

We  found  in  these  experiments  that  the  results  were  not 
affected  by  poisoning  the  endothelium  of  the  pleura  either  by 
means  of  sodium  fluoride,  or  by  the  use  of  scalding  water, 
in  striking  contrast  to  the  effects  of  these  measures,  when 
employed  in  experiments  on  intestinal  absorption.  I  give 
on  pages  91  and  92  four  Tables  which  show  the  course  of  the 
absorption  when  solutions  of  different  strength  are  introduced 
into  the  pleural  cavities  with  or  without  the  addition  of 
sodium  fluoride. 

(2)  Absolution  from  Connective  Tissue  SjMces.  —  I  have 
already  dealt  with  the  question  of  interchanges  between  the 
jntravascular  blood  and  the  interstitial  fluid  of  the  tissues 
which  are  conditioned  by  differences  of  concentration  in 
these  two  fluids,  and  we  know  that  fluids  of  any  description 
introduced  into  these  spaces  will  slowly  find  their  way  into 
the  lymphatics  draining  the  part,  especially  if  the  transference 
be  aided  by  active  or  passive  movements  of  the  part.  More- 
over, any  rise  of  pressure  in  the  capillaries  tends  to  produce 
an  increased  amount  of  transudation,  and  therefore  increased 
distension  of  the  tissue  spaces.  The  fluid  which  thus  fills 
these  spaces  is  practically  identical  with  the  blood-plasma, 
except  as  regards  its  protein  content  and  any  changes  in  its 
composition  due  to  the  metabolic  requirements  of  the  cells. 
W^herevej  we  obtain  tissue  fluid  for  examination,  or  the  lymph 


94  THE    FLUIDS    OF    THE    BODY 

coming  from  the  tissue  spaces,  with  the  one  exception  of  the 
liver,  we  find  a  protein  content  far  inferior  to  that  of  the 
blood-plasma. 

The  interchange  between  blood  and  spaces,  so  far  as  regards 
the  fluid,  must  be  reciprocal ;  there  must  be  a  possibility  for 
the  fluid  in  these  spaces  to  get  back  into  the  blood.  What 
mechanisms  are  available  for  this  re-absorption?  Must  all 
the  interstitial  fluid  take  the  slow  and  devious  path  by  way  of 
the  lymphatics  and  thoracic  duct,  or  can  it  pass  directly  back 
through  the  capillary  wall  into  the  circulating  blood  ?  There 
is  no  doubt  that  the  latter  alternative  is  correct  and  that  the 
fluid  can  be  directly  taken  up  from  the  tissue  spaces  into  the 
blood  circulating  through  the  capillaries,  without  the  inter- 
mediation of  the  lymphatics. 

If  an  animal  be  bled  to  a  large  amount,  the  latter  portions 
of  the  blood  obtained  differ  from  the  earlier  portions  in  that 
they  are  more  dilute,  the  blood  containing  fewer  corpuscles 
and  the  separated  plasma  a  smaller  content  in  protein.  The 
fluid  which  has  come  into  the  blood  and  has  effected  its 
dilution  is  derived  from  the  tissues,  and  the  process  represents 
an  attempt  on  the  part  of  the  organism  to  make  up  the  total 
volume  of  the  circulating  fluid  to  its  normal  amount.  The 
drying  of  the  tissues  thereby  produced  is  evidenced  by  the 
extreme  thirst  which  ensues  after  any  severe  haemorrhage  and 
results  in  a  greater  uptake  of  water  from  the  intestine,  so  that 
finally  the  total  quantity  of  fluid,  both  of  blood  and  tissues, 
is  re-established,  long  before  the  organism  has  had  time 
to  make  good  the  shortage  in  red  corpuscles  and  plasma- 
protein. 

This  uptake  of  fluid  from  the  tissues  can  be  shown  to 
be  entirely  independent  of  the  gradual  return  of  the  tissue 
fluid  to  the  blood  by  way  of  the  thoracic  duct.  Artificial 
anaemia  reduces  the  rate  of  flow  from  the  thoracic  duct,  and 


THE    ABSORPTION    OF    THE    INTERSTITIAL    FLUIDS  95 

the  dilution  of  the  blood  observed  after  haemorrhage  is  not 
interfered  with  in  any  way  by  ligature  of  this  duct.  Moreover, 
the  abdominal  viscera  are  not  directly  or  exclusively  concerned 
in  the  process,  since  the  dilution  of  blood  as  a  result  of 
hsBmorrhage  may  be  observed  after  a  total  extirpation  of  all 
the  abdominal  viscera.  I  have  shown  by  direct  experiments  * 
that  the  blood  circulating  through  the  connective  tissues  can 
take  up  an  isotonic  fluid  present  in  the  meshes  of  these  tissues. 
The  experiment  was  carried  out  as  follows : — 

The  blood  of  a  dog  was  defibrinated  intra  vitam,  by  bleeding, 
whipping,  and  reinjecting  the  blood  five  or  six  times.  (This 
was  to  avoid  the  danger  of  capillary  clots  during  the  subse- 
quent experiment.)  The  dog  was  then  bled  to  death,  and 
cannulas  inserted  in  the  femoral  arteries  and  veins  on  both 
sides.  The  right  leg  w^as  then  made  oedematous  by  the  injec- 
tion of  1  per  cent,  or  1'05  per  cent.  NaCl  solution  into  the 
connective  tissues  by  means  of  a  needle.  Part  of  the  blood 
which  had  been  obtained  having  been  set  aside  for  subsequent 
analysis,  tlie  rest  w^as  divided  into  two  equal  parts.  One- 
half  was  then  led  through  each  limb  at  a  pressure  varying 
betw^een  65  and  85  mm.  Hg.  By  means  of  an  arrangement 
of  tubes  and  clamps,  somewhat  similar  to  that  of  Ludwig's 
*  Stromaiche,'  it  was  possible,  as  soon  as  all  the  blood  had 
been  led  through,  to  start  the  circulation  afresh  from  the 
bottle  which  had  been  previously  connected  with  the  vein. 
I  was  thus  carrying  on  two  experiments  (one  of  them  being 
a  control)  at  the  same  time.  Each  half  of  the  blood  was  led 
through  one  leg  from  12  to  25  times.  The  experiment  was 
then  stopped,  and  the  solids  in  the  whole  blood  and  in  the 
serum  of  the  three  samples  of  blood  were  estimated,  as  well 
as  the  relative  amounts  of  haemoglobin  in  each.    It  w^as  found 

-  Journ.  of  Flnjsiol.,  XIX.,  312,  1896, 


96 


THE    FLUIDS    OF    THE    BODY 


that  the  blood,  which  had  been  led  through  the  normal 
leg  from  12  to  25  times,  was  either  unaltered,  or,  in  most 
cases,  had  undergone  slight  concentration.  The  blood, 
which  had  been  led  the  same  number  of  times  through 
the  oedematous  leg,  had  in  all  cases  absorbed  fluid ;  both 
the  whole  blood  and  the  serum  were  more  dilute  and  the 
haemoglobin  percentage  was  diminished.  In  these  experi- 
ments the  freezing  points  of  the  blood  serum  and  of  the  fluid 
injected  to  form  the  oedema  were  estimated,  and  care  was 
taken  to  ensure  that  the  osmotic  pressure  of  the  injected  fluid 
was  not  below  that  of  the  blood-serum,  so  that  the  absorp- 
tion of  fluid  could  not  be  explained  by  ordinary  osmotic 
processes.  I  give  here  Tables  showing  the  results  of  these 
experiments. 


Solids  of  Blood  per  cent. 

Hsemoglobin  (standard  =  100). 

No.  of 
experiment. 

standard. 

From  normal 
leg. 

From 
oedematous  leg. 

Blood  from 
normal  leg. 

Blood  from 
oedematous  leg. 

I. 

21-00 

21-08 

19-98 

— 

— 

n. 

18-9 

19-2 

18-0 

— 

— 

III. 

22-2 

22-2 

21-4 

— 

— 

IV. 

lost 

20-1 

19-4 

— 

— 

Y. 

20-6 

(no  control) 

20-00 

— 

— 

VI. 

21-26 

21-42 

20-56 

100 

97 

VII. 

19-97 

20-66 

19-75 

104 

96 

VIII. 

20-7 

21-2 

20-00 

103 

95 

IX. 
X. 


21-12 
19-5 


Tiuo  experiments  tuith  Serum. 


21-08 
19-9 


21-09 
19-7 


102 


102 


THE    ABSORPTION    OF    THE    INTERSTITIAL    FLUIDS 


97 


Solids  of  Serum  and  Freezing  Points. 


Standard. 


(Edematous 


A  =  -  -600 


6*6  per  cent. 
A  =  —  -635 


7*2  per  cent. 
/\=  -  -640 


Composition  of  redema 
fluid  and  freezing  point. 


8-28  per  cent. 
A  =  -  -64 


A 


•615 


6*1  per  cent.       1  per  cent.  NaCl 
A  =  -  -635       A  =  -  -eiO^C. 

1  per  cent.  NaCl 


No.  of  times 

blood 

transfused 

through  legs. 


6*7  per  cent. 


7*71  percent. 
A  =  -  -64 


1  per  cent.  NaCl 

A  ==  -  -eio^c. 

I'Oo  per  cent.  NaCl 
I'Oo  per  cent.  NaCl 
I'l  per  cent.  NaCl 
1*1  per  cent.  NaCl 

A  =  -  -eeo^c. 


_         no  '  1'03  per  cent.  NaCl 
^  ~  ~         I     A  =  -  •640°C. 


12  times 

16      „ 

12      „ 

12 
12 
20 

24      „ 
20      „ 


Two 

experiments  tuith  serum. 

— 

A  = 

-  -605 

A  =  -  '605 

Ox  serum. 
A  =  -  -oSO^C. 

15 

>> 

— 

A  = 

-  -645 

A  =  -  -635 

Ox  serum. 

A  =  -  -oSo^C. 

15 

>> 

From  these  experiments,  we  may  affirm  with  certainty 
that  isotonic  salt  sokitions  can  be  taken  up  directly  by  the 
blood  circulating  in  the  blood  vessels. 

The  Mechanism  of  Absorption. 

We  have  now  to  consider  how  this  absorption  is  effected. 
Are  the  capillary  walls  so  constituted  as  to  react  to  a  lowering 
of  the  capillary  pressure  with  an  active  absorption  of  the 
extravascular  fluid,  i.e.,  is  the  absorption  due  to  the  vital 
activity  of  the  cells  ?  Or  can  we  find  mechanical  conditions 
that  will  account  for  this  absorption  ? 

F.B,  H 


98  THE    FLUIDS    OF    THE    BODY 

The  first  possibility  that  will  strike  anyone  working  at  the 
subject  is  that  the  absorption,  like  the  transudation  of  fluid, 
may  be  effected  by  a  process  analogous  to  filtration,  Landerer* 
estimated  the  tissue  tension  at  half  to  three-quarters  of  that 
existing  in  the  capillaries.     It  is  evident  that,  if  such  were  the 
case,   any  considerable  fall  of   intracapillary  pressure  would 
bring  it  below  the  tissue-pressure,  and  a  back-filtration  into 
the  vessels  might  occur.  Some  experiments  of  Klemensiewiez,t 
with  regard  to  the  mechanical  effects  of  oedema  on  the  circula- 
tion, might  be  quoted  against  this  hypothesis.     This  latter 
observer  led  fluid  through  a  piece  of  intestine  enclosed  in  an 
outer    tube    of    glass.      He    found  that    at    first    there  was 
transudation  outwards  through  the  intestinal  wall  and  a  rise 
of   pressure   in  the   glass   tube.     As    soon    however   as   the 
pressure   in   the   outer   tube  reached  that  obtaining  at  the 
venous   end   of   the   model   capillary,    this    latter   collapsed. 
Exudation  continued  from  the  arterial  end  of  the  capillary. 
The    pressure    therefore    rose    higher    and.   higher    in    the 
outer  tube  until  the  exuded  fluid  had  caij^p  collapse  of  the 
greater  part  of  the  intestinal    tube.      I^^^oncluded  that  a 
similar  sequence  of  events  would  take  place  in  oedema,  and 
that  the  exuded  fluid  would  tend  to  compress  the  veins,  raising 
the  pressure  in  the  capillaries  still  higher  and  increasing  the 
exudation.     A  vicious  circle  was  thus  established,  which  ended 
only  with  the  complete  arrest  of  the  circulation  through  the 
part  affected. 

This  objection  of  Klemensiewiez  to  the  possibility  of  filtra- 
tion backwards  holds  good  only  if  the  structural  relations  in 
the  connective  tissues  are  similar  to  the  arrangement  of  his 

*  ' '  Die  Gewebsspannung  in  ihrem  Einjluss  auf  die  ortliche  Blut-und 
Lymph-be wegung,"  Leipzig,  1884. 

t  "  Sitzb.  der  k.  Akad.  der  Wissensch,"  LXXXIV.,  1881,  and  XOIY., 

1886. 


THE    ABSORPTION    OF    THE    INTERSTITIAL    FLUIDS  99 

mechanical  model.  If  however  the  capillaries,  instead  of 
running  freely  through  the  connective  tissue  spaces,  are 
bound  to  the  walls  of  these  spaces  by  an  adventitia  of  radiating 
fibres,  a  rise  of  pressure  in  the  spaces  above  that  obtaining  in 
the  capillaries  will  not  collapse  these  latter,  but  will  rather 
tend  to  dilate  them ;  and  filtration  back  into  the  capillary 
would  be  structurally  possible.  If  sections  be  cut  of  injected 
oedematous  connective  tissues,  it  will  be  seen  that  the  capil- 
laries are  surrounded  and  supported  by  such  an  adventitia  of 
radiating  fibres,  and  have  in  fact  a  structure  very  similar  to 
that  figured  by  Eanvier*  in  the  lymphatic  gland  and  by 
Heidenhain  f  in  the  section  through  a  villus.  In  the  veins 
however,  no  such  arrangement  can  be  seen,  all  the  fibres 
surrounding  these  tubes  being  apparently  disposed  concentric- 
ally. From  a  purely  anatomical  study,  it  would  seem  there- 
fore that  a  filtration  back  into  the  capillaries  is  possible,  pro- 
vided that  the  rise  of  pressure  in  the  tissue  spaces  does  not 
extend  to  the  tissues  surrounding  the  larger  veins.  The 
question  whether  filtration  back  into  the  vessels  is  or  is  not 
possible  from  the  connective  tissues  in  most  parts  of  the  body 
can  be  only  definitely  solved  by  physiological  experiment. 

I  found  that,  when  fluid  was  injected  into  the  connective 
tissues  of  the  leg,  the  outflow  from  the  veins  of  the  leg 
diminished,  showing  that  a  rise  of  pressure  in  these  spaces 
causes  collapse  of  the  big  veins,  and  therefore  increased  pres- 
sure in  the  peripheral  veins  and  ca^Dillaries  (Fig.  8).  Similar 
results  were  obtained  on  injecting  fluid  into  the  interstices  of 
a  muscular  organ  such  as  the  tongue,  or  of  a  glandular  struc- 
ture such  as  the  submaxillary  gland ;  so  we  may  conclude 
that  absorption  of  fluid  by  the  blood  vessels  by  a  process  of 

-''  "  Teclmisclies  Lehrbuch  der  Histologie  "  (Nicati  und  Wvss),  Fig,  208, 
1877. 

t  Cp.  ''  Quain's  Anatomj,"  lOth  ed.,  III.,  Pt.  4,  Fig.  110. 

H   2 


100  THE  FLUIDS  OF  THE  BODY 

backward  filtration  is  impossible  in  the  subcutaneous  connec- 
tive tissues  of  the  limbs,  in  muscles,  and  in  all  glandular 
structures  which  have  an  analogous  build  to  the  submaxillary 
gland.  Theoretically  we  may  say  that  absorption  by  filtra- 
tion is  possible  only  in  those  regions  of  the  body  where  a 
sudden  rise  in  tissue-pressure  will  not  be  propagated  to  the 
neighbourhood  of  the  large  veins.  Such  regions  might  be 
found  in  the  cutis  itself  or  in  the  intestinal  villus,  but  such 


Southey  tube  0.     ,  .    ,.      T.  Cannula  to  Manometer 
'  Injecting 


Southey  tube  C 


Fig.  8. — Diagram  to  show  arrangement  of  experiment  on  absorption 
of  fluid  by  tbe  blood-vessels. 

By  the  injecting  needle  fluid  was  injected  into  the  subcutaneous 
tissue,  and  the  pressure  of  the  oedema  fluid  thus  produced  was  measured 
by  means  of  manometers  attached  to  the  two  Southey's  tubes  (small 
perforated  silver  tubes). 

The  flow  through  the  vein  was  measured  by  allowing  the  blood  to  drop 
from  its  proximal  end  on  to  a  drop  counter,  while  changes  in  the 
pressure  peripheral  to  the  oedema  were  determined  by  a  manometer 
attached  to  a  _L  cannula  inserted  into  a  vein  of  the  foot. 

minute  spaces  are  not  at  present  accessible  to  our  experi- 
mental methods  of  investigation.  So  far  as  our  results  go, 
reabsorption  by  a  process  of  back-filtration  must  be  excluded. 
There  is  however  another  factor  present  which  would  aid 
absorption  of  fluid  by  the  blood  vessels,  and  might  therefore 
account  for  the  reabsorption  of  the  tissue  fluid  which  occurs 
after  haemorrhage,  or  when  the  general  blood  pressure  is 
lowered.  In  Lecture  II.  I  called  your  attention  to  the  fact 
that  the  non-diffusible  constituents  of  the  blood  serum,  chiefly 


THE    ABSORPTION    OP    THE    INTERSTITIAL    FLUIDS  101 

proteins,  were  capable  of  exercising  an  osmotic  pressure  or 
osmotic  attraction  for  water,  which  amounted  to  about  4  mm. 
Hg.  for  every  1  per  cent,  protein  in  the  serum.  Blood-plasma 
with  6  to  8  per  cent,  proteins  would  therefore  exert  an  osmotic 
pressure  of  25  to  30  mm.  Hg.  as  compared  with  an  isotonic 
salt  solution.  The  importance  of  these  results  lies  in  the  fact 
that,  although  the  osmotic  pressure  of  the  proteins  of  the 
plasma  is  so  insignificant  when  contrasted  with  that  of  its 
saline  constituents,  it  is  of  an  order  of  magnitude  comparable 
to  that  of  the  capillary  blood  pressure ;  and  whereas  capillary 
pressure  is  the  chief  determining  factor  in  the  production  of 
interstitial  fluid,  the  osmotic  difference  of  pressure  dependent 
on  the  greater  concentration  of  the  fluid  within  as  compared 
with  that  without  the  blood  vessels  might  be  sufficient  to  deter- 
mine absorjDtion.  In  fact  the  osmotic  attraction  of  the  serum, 
or  plasma,  for  the  extravascular  fluid  will  be  proportional  to 
the  forces  expended  in  the  production  of  the  latter,  so  that  at 
any  given  time  there  may  be  a  balance  between  the  hydro- 
static pressure  of  the  blood  in  the  capillaries  and  the  osmotic 
attraction  of  the  blood  for  the  surrounding  fluids.  With 
increased  capillary  pressure  there  must  be  increased  transuda- 
tion. The  blood  will  become  more  concentrated  until  equili- 
brium is  established  at  a  somewhat  higher  point,  when  there 
is  a  more  dilute  fluid  in  the  tissue  spaces  and  therefore  a 
higher  absorbing  force  to  balance  the  increased  caj)illary 
pressure.  With  diminished  capillary  pressure  there  will  be 
an  osmotic  absorption  of  salt  solution  from  the  extravascular 
fluid;  this  becomes  richer  in  proteins,  and  the  process  will 
come  to  an  end  when  the  difference  between  its  protein  osmotic 
pressure  and  that  of  the  intravascular  plasma  is  equal  to  the 
diminished  capillary  pressure. 

It  is  evident  that  this  mechanism  will  not  account  for  the 
absorption  of  serum,  or  other  fluid  rich  in  proteins,  from  the 


102  THE  FLUIDS  OF  THE  BODY 

serous  cavities  and  connective  tissue  spaces.  It  is  difficult 
however  to  get  satisfactory  evidence  that  such  fluids  are 
absorbed  by  the  blood  vessels.  Serum,  when  injected  into 
the  pleural  cavity,  is  absorbed,  with  such  slowness  that  it  is 
impossible  to  exclude  the  possibility  that  the  whole  of  the 
absorption  has  taken  place  by  way  of  the  lymphatics.  In  two 
experiments,  in  which  I  made  the  hinder  limb  of  an  animal 
oedematous  by  the  injection  of  serum  instead  of  salt  solution 
(Cp.  Table,  p.  96),  I  could  obtain  no  evidence  of  absorption 
of  the  oedema  fluid  by  the  blood  vessels. 

It  ought  to  be  possible  to  determine  experimentally  whether 
the  mechanical  processes  which  I  have  described  suffice  to 
explain  the  whole  of  the  interchange  between  the  blood  and 
the  tissues.  I  have  indeed  instituted  certain  experiments  in 
this  direction,  but  have  not  yet  obtained  sufficiently  definite 
results  on  account  of  the  complexity  of  the  factors  involved. 
It  would  seem  however  that  the  experimental  test  might  be 
applied  somewhat  as  follows  : — 

Absorption  by  the  blood  vessels  as  a  result,  say  of  artificial 
haemorrhage,  if  determined  entirely  by  the  osmotic  attraction 
of  the  plasma  colloids  for  the  extravascular  fluid,  can  only 
bring  about  a  passage  of  water  and  salts  into  the  blood  vessels. 
We  know  that  after  bleeding  the  blood-serum  becomes  more 
watery,  i.e.,  its  proteins  diminish.  By  ascertaining  the  total 
volume  of  circulating  blood  and  the  change  in  its  hsemoglobin 
content  after  bleeding,  as  well  as  the  relative  proportion  of 
corpuscles  to  plasma,  we  could  find  the  absolute  volume  of  the 
fluid  which  has  passed  from  tissue  spaces  into  blood  vessels. 
According  to  my  explanation  this  fluid  should  be  pure  salt 
solution.  That  it  is  more  dilute  than  plasma  is  clearly 
shown  by  experiments,  but  our  data  do  not  yet  suffice  to  decide 
whetlier  the  incoming  fluid  is  a  weak  solution  of  protein,  such 
as   that   contained   in   the   tissue    spaces,   or  is  a  pure  salt 


THE    ABSORPTION    OF    THE    INTERSTITIAL   FLUIDS  103 

solution.  If  it  is  proved  by  quantitative  results  to  contain 
protein,  then  some  other  factor,  such  as  back-filtration  or 
active  absorption  by  the  endothelial  cells  of  the  blood 
vessels,  must  be  involved  in  addition  to  the  attractive 
forces  exercised  by  the  colloid  constituents  of  the  circulating 
blood. 


LECTURE  VI 


THE    OUTPUT    OF    FLUID 


Foe  the  normal  functions  of  the  body  constancy  of  medium 
is  essential.  The  maintenance  of  this  constancy  is  determined 
partly  by  the  regulation  of  the  intake  through  the  intermedia- 
tion of  the  nervous  system.  The  chief  ganglionic  masses  of 
the  organism  have  for  this  reason  been  aggregated  especially 
at  its  mouth  end,  and  their  regulating  power  over  the  intake 
grows  with  the  gradual  increase  in  the  complexity  of  their 
reactions  coincident  with  their  development  into  the  brain  of 
the  higher  animals.  If  we  cut  away  the  functions  of  appetite, 
which  we  may  locate  in  the  cerebral  cortex,  and  probably  in 
the  deeper  cells  of  this  structure,  the  regulation  of  intake  is 
largely  interfered  with. 

The  alimentary  canal,  apart  from  the  nervous  regulation  of 
the  oral  aperture,  has  but  little  power  of  adapting  its  activities 
to  the  needs  of  the  body  as  a  whole.  It  is  true  that  substances 
which  may  be  regarded  as  more  or  less  normal,  e.g.,  sugar  and 
sodium  chloride,  are  absorbed  with  greater  facility  than 
substances  such  as  sodium  sulphate  or  potassium  iodide,  which 
do  not  form  necessary  constant  ingredients  of  the  body.  The 
difference  is  only  one  of  degree,  and  the  absorption  of  these 
substances  themselves  may  continue,  although  there  may  be 
already  a  greater  amount  of  them  in  the  organism  as  a  whole 
than  it  actually  requires. 

The  injurious  results  of  any  indiscriminate  activity  on  the 
part  of  the  alimentary  canal  are  counteracted  by  one  of  the 
chief  organs  which  effect  the  output  of  fluid,  viz.,  the  kidneys. 


THE    OUTPUT    OF    FLUID  105 

Water  is  lost  to  the  body  by  means  of  the  lungs ;  water  and 
dissolved  substances  by  the  skin.  In  neither  of  these  cases 
is  the  output  of  water  determined  by  the  water  balance  of  the 
body.  The  presence  of  aqueous  vapour  in  the  expired  air  may 
be  regarded  as  an  accident  of  the  structure  of  the  respiratory 
organs,  and  the  output  of  water  by  this  means  is  conditioned 
by  the  frequency  and  depth  of  respiration,  and  therefore  by 
the  needs  of  the  organism  for  oxygen.  The  output  of  water 
by  the  skin  represents  a  means  by  which  the  organism 
maintains  a  constant  body  temperature,  and  is  determined 
entirely  by  the  amount  of  heat  produced  in  the  body  in 
relation  to  the  temperature  of  the  surrounding  air.  In  the 
kidneys  we  find  an  organ  whose  function,  broadly  speaking, 
is  the  regulation  of  the  amount  and  composition  of  the  total 
fluid  of  the  body :  a  regulation  which  it  is  able  to  carry  out 
in  consequence  of  its  sensitiveness  to  minute  changes  in  the 
composition  and  amount  of  the  blood  circulating  through  its 
vessels. 

Thus  in  the  normal  individual  the  kidneys  put  out  every 
day  about  1,500  cc.  of  a  fluid  containing  all  the  soluble* 
waste  products  resulting  from  the  nitrogenous  metabolism  of 
the  tissues  during  the  last  twenty-four  hours,  as  well  as  all 
the  salts  which  have  been  taken  up  in  the  food  and  have 
passed  through  the  body  without  being  needed  for  storage  in 
any  growing  tissue. 

Since  the  concentration  of  urine  may  be  many  times  higher 
than  that  of  blood,  its  freezing  point  varying  from  2°  to  4° 
below  zero,  it  is  evident  that  a  considerable  amount  of  energy 
must  be  expended  by  the  kidney  in  its  production.  Neither 
the  concentration  nor  the  composition  of  the  urine  is  constant. 
In  this  fluid  we  find  all  the  soluble  waste  products  in  what- 
ever amount  they  have  been  produced.  In  it  we  .find  also  any 
substances  which  .have  made  their  way  into  the  blood  through 


106  THE  FLUIDS  OF  THE  BODY 

the  alimentary  canal  and  are  not  required  for  the  needs  of  the 
organism,  as  well  as  normal  constituents  of  the  body  so  soon 
as,  for  one  reason  or  another,  they  accumulate  in  the  blood 
above  their  ordinary  concentration.  The  function  of  the 
kidney  is  to  keep  the  composition  of  the  circulating  fluid 
constant,  and  we  can  therefore  alter  the  urine  in  any  direc- 
tion according  to  the  nature  of  the  change  which  we  bring 
about  in  the  composition  of  the  body.  Thus  the  chief  salt 
of  normal  urine  is  sodium  chloride.  If  an  animal  be  deprived 
of  sodium  chloride  in  its  food,  this  salt  practically  disappears 
from  the  urine  long  before  any  change  can  be  detected  in  the 
sodium  chloride  content  of  the  plasma.  If  we  drink  large 
amounts  of  water,  we  do  not  produce  any  great  lowering  of 
the  molecular  concentration  of  the  plasma,  or  any  great 
increase  in  the  volume  of  the  circulating  blood.  As  fast  as 
the  water  is  absorbed  from  the  alimentary  canal,  it  is  picked 
up  by  the  kidneys  and  passed  out  into  the  urine,  which 
becomes  extremely  dilute  with  a  molecular  concentration 
far  below  that  of  the  blood.  The  kidney  therefore  presents 
m  the  highest  degree  the  phenomenon  of  'sensibility,'  the 
power  of  reacting  to  various  stimuli  in  a  direction  which 
is  appropriate  for  the  survival  of  the  organism :  a  power  of 
adaptation  which  almost  gives  one  the  idea  that  its  component 
parts  must  be  endowed  with  intelligence. 

When  however  we  extend  our  investigations  on  the 
functions  of  these  organs,  we  come  across  a  whole  set  of 
conditions  in  which  this  intelligent  adaptation  suddenly  makes 
default,  in  which  the  secretory  activity  of  the  kidney  is 
apparently  aroused  by  purely  mechanical  conditions  without 
reference  to  or  in  direct  opposition  to  the  needs  of  the  organism 
as  a  whole.  Thus  the  injection  of  a  concentrated  salt  solution, 
e.g.,  10  per  cent,  sodium  sulphate,  or  sodium  chloride,  into  the 
circulation  produces  a  copious  flow  of  urine  which  is  not  only 


THE    OUTPUT    OF    FLUID  107 

less  concentrated  than  that  of  the  injected  fluid,  but  is  less 
concentrated  than  the  normal  urine,  although,  by  the  injection 
of  the  salt  solution,  the  molecular  concentration  of  the  body 
as  a  whole  is  increased.  Change  in  the  blood  flow  through 
the  kidney  may  bring  about  alterations  in  the  flow  of  urine 
quite  irrespective  of  the  composition  of  the  blood  or  of  the 
tissues. 

The  occurrence  of  these  two  classes  of  phenomena  seems  to 
be  determined  by  the  fact  that  the  kidney  is  a  dual  organ,  and 
that  while  one  part  of  it  acts,  so  to  speak,  passively  in  response 
to  force  impressed  upon  it  from  without,  another  part,  endowed 
with  sensibility,  reacts  to  external  forces  in  a  direction  which 
may  be  opposed  to  these  forces,  but  is  in  all  cases  the 
appropriate  one  for  the  welfare  of  the  whole  organism. 

This  dual  nature  of  the  kidney's  activity  has  formed  the 
basis  of  all  our  views  on  the  physiology  of  this  organ,  since  its 
histology  was  first  investigated  by  Bowman  and  by  Ludwig,  and 
attention  was  drawn  to  the  marked  differences  in  structure 
and  arrangement  of  the  glomeruli  at  the  beginning  of  the 
renal  tubules  and  of  the  cells  lining  the  rest  of  these  tubules. 
Such  a  marked  difl'erence  in  structure  must  determine  differ- 
ence in  function,  and  it  is  therefore  customary  to  treat 
separately  the  functions  of  the  glomeruli  and  the  functions 
of  the  tubules.  Opinions  as  to  the  different  parts  played  by 
these  two  sets  of  structures  are  still  widely  divergent,  and 
we  cannot  expect  to  attain  any  general  agreement  among 
physiologists  until  some  method  shall  have  been  devised  for 
investigating  the  functions  of  one  of  them  apart  from  the 
other.  I  may  follow  here  the  general  custom  and  discuss 
the  mechanism  of  the  kidney's  activity  under  these  two 
headings. 

Functions  of  the  Glomeruli. — It  is  generally  assumed,  as  the 
best  explanation  of  known  facts  with  regard  to  the  secretion 


108  THE  FLUIDS  OF  THE  BODY 

of  urine,  that  a  dilute  saline  exudation  free  from  protein  is 
formed  in  the  glomeruli  and  that  it  becomes  concentrated  on 
its  way  through  the  tubules  either  by  the  absorption  of  water 
and  certain  salts  or  by  the  secretion  and  addition  of  urea, 
uric  acid,  etc.,  as  well  as  of  such  salts  as  acid  phosphates. 

As  to  the  nature  of  the  glomerular  functions  two  opinions 
have  been  held.  According  to  the  Ludwig  School  the  process 
is  one  simply  of  filtration,  in  which  under  the  pressure  of  the 
blood  in  the  glomerular  capillaries  the  water  and  crystalloid 
constituents  of  the  plasma  are  filtered  through  the  glomerular 
ej)ithelium,  leaving  behind  the  protein  constituents.  Accord- 
ing to  Heidenhain  the  process  cannot  be  regarded  as  one 
simply  of  filtration  but  involves  the  secretory  activity,  i.e.,  the 
doing  of  work  on  the  part  of  the  glomerular  epithelium. 

If  the  glomerular  urine  is  a  filtrate  it  must  resemble  blood- 
plasma  in  practically  all  particulars  except  its  protein  content, 
since  the  blood  pressure,  which  is  the  only  force  causing 
filtration,  is  too  small  to  effect  any  appreciable  separation  of 
salts.  On  the  other  hand,  a  certain  minimum  difference  of 
pressure  between  the  two  sides  of  the  membrane  must  be 
present  in  order  to  separate  the  colloids  from  the  other 
constituents  of  the  plasma.  In  an  earlier  lecture  I  have 
shown  that  1  per  cent,  of  proteins  in  the  serum  corresponds  to 
about  4  mm.  Hg.  pressure,  so  that  blood  serum  containing 
7  to  8  per  cent,  of  proteins  would  possess  an  osmotic 
pressure,  due  to  its  colloidal  content,  of  25  to  30  mm.  Hg. 
In  order  to  produce  a  filtrate,  free  from  protein,  from  the 
blood-plasma  circulating  through  the  glomerular  capillaries, 
a  minimum  difference  of  pressure  of  between  30  and  40 
mm.  Hg.  will  be  necessary,  i.e.,  the  pressure  of  the  urine  in 
the  tubules  and  ureter  must  always  be  at  least  30  mm.  Hg. 
lower  than  the  pressure  of  the  blood  in  the  glomeruli.  A 
direct  determination  of  the  latter  figures  is  not  possible.     But 


THE    OUTPUT    OF    FLUID  109 

the  anatomical  arrangements  are  such  as  to  bring  this  pressure 
up  to  a  high  point.  Not  only  are  the  vasa  afferentia  very 
short  but  their  diameter  is  one-third  greater  than  that  of  the 
vasa  efferentia.  Moreover  the  sudden  increase  of  bed  which 
ensues  as  the  blood  passes  from  vas  afferens  to  the  bundle 
of  capillaries  must  itself  cause  a  rise  of  pressure  in  the  latter, 
due  to  the  transformation  of  the  kinetic  energy  of  the  moving 
fluid  into  the  statical  energy  represented  by  pressure  on  the 
walls  of  the  vessels. 


— * 

h 

Fig. 

9. 

This  point  can  be  rendered  clearer  by  the  following  considerations.  If 
a  fluid  is  flowing  in  a  tube  of  continuous  bore  a  h,  there  will  be  a  con- 
tinuous fall  of  pressure  from  a  to  h.  If,  however,  in  the  tube  a  he  (Fig.  9) 
the  segment  h  be  of  much  greater  diameter  than  the  segments  a  and  c, 
although,  while  the  fluid  is  at  rest,  the  pressures  will  be  equal  at  all 
points  of  the  system,  as  soon  as  the  fluid  moves  from  a  to  c,  there 
is  a  fall  of  pressure  between  a  and  c,  but  a  manometer  attached  to  h  may 
show  an  actually  greater  pressure  than  a  manometer  inserted  at  a. 
Apparently  therefore  fluid  is  flowing  from  the  place  of  lower  to  a 
place  of  higher  pressure.  The  apparent  paradox  is  due  to  the  fact 
that  the  energy  causing  the  fluid  to  move  from  a  to  &  is  of  two  kinds. 
It  equals  ^  mv^  +  P,  i.e.,  is  represented  by  the  kinetic  energy  of  the 
m.oving  mass  of  fluid  as  well  as  the  difference  of  pressure  between  any 
two  points  of  the  tube.  The  total  energy  will  diminish  continuously  from 
a  to  c,  and  is  used  in  overcoming  the  resistance  of  the  system.  We  may 
say  then  that  the  simi  of  these  two,  namely,  ^  mv^  +  P  is  greater 
at  a  than  h,  and  is  greater  at  h  than  c.  But  as  the  fluid  passes  from  the 
narrow  tube  a  into  the  wide  tube  h,  there  is  a  sudden  fall  of  its  velocity 
and  a  consequent  diminution  of  the  factor  ^  mv^.  In  order  then  to  pro- 
vide for  a  continuous  fall  in  the  total  energy  of  the  fluid,  namely,  ^  mv^  +  Pj 
the  diminution  in  the  factor  ^  mv^  must  cause  a  corresponding  increase 
in  the  factor  P,  i.e.,  in  the  lateral  pressure  exercised  by  the  fluid  on  the 
vessel  wall.  As  the  total  diameter  of  the  bed  of  the  stream  in  the  capil- 
laries may  be  twenty  tijnQs    th^g^t  of  the  bed  in  the  vas  afferens,  the 


110  THE  FLUIDS  OF  THE  BODY 

velocity  of  the  1)100(1  in  these  capillaries  will  he  only  ^^  of  that  in  the 
artery,  and  the  kinetic  energj^  of  the  blood  only  ^^■^.  It  is  possible  there- 
fore that  the  pressure  exercised  by  the  blood  on  the  walls  of  the  capillaries 
may  be  even  greater  than  that  in  the  interlobular  arteries,  and  this  effect 
will  be  still  further  aided  by  the  narrow  diameter  of  the  vas  efferens. 
Although  the  pressure  in  the  ordinary  capillaries  of  the  body  is 
probably  not  greater  than  20  to  30  mm.  Hg.,  the  glomerular  capillaries 
might  present  a  pressure  little  inferior  to  that  in  the  main  arteries  of  the 
body. 

The  pressure  in  the  ureter  is  under  normal  circumstances 
approximately  nil,  whereas  that  in  the  glomerular  capillaries 
is  probably  not  more  than  20  mm.  Hg.  below  that  in  the  main 
arteries  of  the  body,  so  that  there  is  a  difference  of  pressure  on 
the  two  sides  of  the  membrane  more  than  sufficient  to  cause  a 
constant  filtration  of  a  protein-free  fluid  from  the  blood-plasma 
coursing  through  these  caiDillaries.  On  raising  the  pressure 
on  the  tubule  side,  the  filtration  ought  to  come  to  an  end  when 
the  pressure  approaches  a  figure  which  is  within  30  to  40  mm. 
of  that  in  the  glomeruli.  A  number  of  observers  have  found 
that  urinary  formation  comes  to  an  end  when  the  blood  pres- 
sure falls  to  between  40  and  50  mm.  Hg.  In  the  same  way 
the  urinary  secretion  ceases  if  the  pressure  in  the  tubules  be 
raised  by  means  of  ligature  of  the  ureter.  Under  these 
circumstances  it  is  found  that  urinary  secretion  continues 
for  a  time  until  the  pressure  in  the  ureter  rises  up  to  a 
certain  point.  In  one  experiment*  the  following  pressures 
were  obtained  in  a  dog  which  was  secreting  urine  copiously 
under  the  action  of  diuretin.  Manometers  were  connected 
both  with  the  carotid  artery  and  with  the  ureters.  The  latter 
were  tjien  ligatured. 


Arterial  pressure. 

Ureter  pressure.    . 

140 

..72 

138 

92 

133 

88 

Starling,  Journ.  of  Physiol.,  XXIV.,  317,  1899. 


THE    OUTPUT    OF    FLUID  111 

In  this  experiment  secretion  came  to  an  end  with  a 
difference  of  pressure  between  ureter  and  arteries  of  about 
40  to  50  mm.  Hg. 

The  absolute  pressure  attained  within  the  ureter  in  any  given  experi- 
ment after  ligature  of  this  tube  will  vary  with  several  factors.  In  the 
first  place  if  the  minimum  secreting  prcssui-e  is  really  conditioned  bj^  the 
colloid  content  of  the  blood-plasma,  jt  will  bo  less  the  smaller  the 
proportion  of  colloids  in  the  plasma.  In  one  experiment"^  a  flow  of 
urine  was  observed  with  a  blood  pressure  as  low  as  18  mm.  llg.,  but 
in  this  case  the  blood  was  extremely  diluted  as  the  result  of  the  continuous 
injection  into  the  blood  vessels  of  normal  salt  solution. 

On  the  other  hand,  the  ureters,  or  at  any  rate  the  urinarj'-  tubules, 
cannot  be  regarded  as  absolutely  water-tight.  Not  only  are  the  cells 
of  these  tubules  capable  of  taking  np  fluid,  but  it  is  jn-obable  that  at  high 
pressure  a  certain  amount  of  actual  filtration  takes  place  between  the 
cells.  This  process  of  re-absorj)tion  will  tend  to  diminish  the  actual 
pressure  of  the  fluid  in  the  ureters,  so  that  the  secretion  of  urine  may 
apparently  come  to  a  standstill  when  there  is  still  a  difference  of  pressure 
between  blood  and  urine  considerably  over  60  mm.  Hg.  Under  such 
circumstances  the  ureter  pressure  will  be  higher  and  the  difference  of 
pressure  between  urine  and  blood  less,  the  more  rapid  the  formation 
of  urine  by  the  glomeruli.  In  a  number  of  experiments  bj^  V.  E.  Ilen- 
dersont  it  was  found  that  the  figure  B.P.  — U.P.  tended  to  approximate 
40  mm,  Hg.  the  more  rapid  the  secretion  of  urine  was.  With  a  slow  secretion 
the  flow  of  urine  apparently  came  to  a  stop  when  there  was  as  much  as 
80  mm.  difference  of  pressure  on  the  two  sides  of  the  glomerular  membrane. 

We  may  conchide  that  for  the  production  of  any  urine  by 
the  kidney  a  certain  minimum  difference  of  pressure  is  neces- 
sary between  the  blood  in  the  glomeruli  and  the  urine  in  the 
tubule,  and  that  this  difference  becomes  less  the  smaller  the 
protein  content  of  the  blood.  Since  the  only  work  required 
in  the  formation  of  a  protein-free  filtrate  from  the  blood  is 
that  due  to  the  osmotic  pressure  of  the  proteins  themselves, 
and  the  observed  difference  of  pressure  during  secretion  is 
greater  than  this  osmotic  pressure,  we  are  justified  in  con- 
cluding, provisionally  at  any  rate,  that  the  mechanical  factors 

*  Gottlieb   u.    Magnus,  Schmiedebey's  Archiv,  XLV.  248,   1901. 
t  V.  E.  Henderson,  Journ,  of  Physiol,,  XXXIII.  175,  1905. 


112  THE  FLUIDS  OF  THE  BODY 

present  at  the  upper  end  of  the  urinary  tubule  are  sufiQcient 
to  account  for  the  production  of  a  glomerular  transudate  free 
from  protein,  but  containing  the  same  proportion  of  water  and 
salts  as  the  blood-plasma  circulating  through  the  capillaries. 

If  the  process  occurring  in  the  glomeruli  is  simply  one  of 
filtration,  three  conditions  must  be  realised. 

(1)  The  amount  of  filtrate,  so  long  as  the  ureter  pressure  is 
constant,  must  depend  on  the  pressure  and  rate  of  flow  of  the 
blood  in  the  glomerular  capillaries,  and  must  fall  or  rise  with 
the  latter. 

(2)  The  constitution  of  the  fully  formed  urine  as  it  appears 
in  the  ureters,  after  modification  by  addition  or  subtraction  on 
the  part  of  the  tubular  cells,  must  approximate  more  closely 
to  the  supposed  glomerular  transudate  containing  the  same 
proportion  of  salts  as  the  blood-plasma,  the  more  rapidly  the 
formation  of  the  glomerular  transudate  takes  place  :  i.e.,  the 
quicker  the  flow  of  urine,  the  more  nearly  must  the  composi- 
tion, reaction,  and  osmotic  pressure  of  the  urine  resemble  that 
of  the  blood  serum. 

(3)  The  total  quantity  of  solids  excreted  in  any  given  time 
must  be  increased  with  any  increase  in  the  urinary  flow.  For 
whatever  the  activity  of  the  tubules,  the  glomeruli  must  blindly 
turn  out  a  certain  ]3roportion  of  solids  with  every  cubic  centi- 
metre of  fluid  that  they  form. 

We  may  deal  first  with  the  influence  of  alterations  in  the 
renal  blood  supply  on  the  flow  of  urine.  Ligature  of  the 
renal  vein  diminishes  and  soon  stops  the  flow  altogether. 
Since  this  procedure  must  cause  a  large  rise  of  pressure  in 
all  the  capillaries  of  the  kidney,  this  result  was  regarded  by 
Heidenhain  as  disproving  any  possibility  of  the  glomerular 
process  being  of  the  nature  of  a  filtration.  At  any  given 
time  however  the  glomeruli  contain  but  little  blood.  With 
total  cessation  of  the  renewal  of  this  blood,  their  contents 


THE    OUTPUT    OF    FLUID 


IIB 


will  rapidly  become  so  concentrated  that  the  capillaries  will  be 
practically  filled  with  a  mass  of  red  corpuscles.  No  filtration 
of  water  and  salts  can  take  place  muless  there  is  a  continual 
renewal  of  the  fluid  on  the  blood  side  of  the  filter. 

On  the  other  hand,  alterations  in  the  blood  supply  to  the 
kidney,  determined  by  changes  on  the  arterial  side,  have  pro- 
nounced effects  on  the  amount  of  urine  formed.  The  pressure 
in  the  glomerular  capillaries  and  the  rate  of  flow  through  these 
capillaries  can  be  increased  in  either  of  two  ways : 

(a)  By  increase  of  the  driving  force,  viz.,  the  general  blood 

pressure. 
(h)  By  a  diminution  of  the  resistance  to  the  flow  of  blood 
through  the  kidneys,  as  by  dilatation  of  the  vessels  of 
this  organ. 
The  results  of  the  experiments  carried  out  on  these  points 
can  be  represented  in  the  following  tabular  form : — 


Procedure. 

General  blood 
pressure. 

Renal  vessels. 

Kidney 
volume. 

Urinary  flow. 

Division  of  spinal  cord 
in  neck 

Palls  to 
40  mm. 

Eelaxed 

Shrinks 

Ceases 

Stimulation  of  cord  .  . 

Eises 

Constricted 

Shrinks 

Diminished 

Stimulation     of     cord 
after  section  of  renal 

Eises 

Passively 
dilated 

Swells 

Increased 

nerves 

Stimulation    of    renal 

Unaffected 

Constricted 

Shrinks 

Diminished 

nerves 

Stim  ulation      of 
splan  clinic  nerve 

Eises 

Constricted 

Shrinks 

Diminished 

Division    of    one 
splanchnic  nerve  : 

a.  In  dog 

b.  In  rabbit 

Unaffected 
Palls 

Dilated 
Eelaxed 

Swells  (?) 
Shrinks  (?) 

Increased 
Diminished 

Plethora 

Eises 

Dilated 

Swells 

Increased 

Haemorrhage  . . 

Palls 

Constricted 

Shrinks 

Diminished 

F.B. 


114  THE  FLUIDS  OF  THE  BOBY 

It  will  be  seen  that  in  every  case,  where  an  increased  blood 
flow  attended  with  a  rise  of  blood  pressure  in  the  glomerular 
capillaries  is  brought  about,  the  urinary  flow  is  at  the  same 
time  increased. 

Another  factor ^  altering  the  ease  with  which  filtration 
of  watery  fluid  and  salts  through  the  glomerular  capillaries 
would  take  place,  would  be  the  composition  of  the  circu- 
lating ]3lasma.  Any  dilution  of  this  plasma  must  render 
filtration  more  easy,  while  a  concentration  would  make  it 
more  difficult.  As  a  matter  of  fact  both  hydrsemia  and 
especially  hydrsemic  plethora,  caused  by  injection  of  normal 
saline  into  the  circulation,  evoke  an  increased  flow  of  urine. 
The  same  effect  occurs  when  the  plethora  is  caused  by  injec- 
tion of  defibrinated  blood,  though  if  the  blood  has  been 
previously  concentrated  by  depriving  the  animals  of  water,  the 
flow  so  caused  is  but  small. 

A  number  of  experiments,  which  have  been  carried  out  on 
the  action  of  diuretics,  have  a  close  bearing  on  the  question  of 
the  nature  of  the  process  occurring  in  the  glomeruli.  A  large 
increase  in  the  urinary  flow  can  be  brought  about  by  the 
intravenous  injection  of  salts,  such  as  sodium  sulphate,  or 
potassium  nitrate,  or  of  neutral  crystalloids  such  as  urea  or 
sugar.  These  bodies  are  often  grouped  together  as  saline 
diuretics.  The  question  arises  whether  the  chemical  changes 
induced  in  the  renal  circulation  by  the  intravenous  injection 
of  sugar  and  salt  solutions  are  sufficient  to  account  for  the 
diuresis.  There  are  three  factors  which  might  be  concerned 
in  promoting  an  increased  glomerular  transudation.  These 
are  : — 

(1)  A  rise  of  pressure  in  the  glomerular  capillaries. 

(2)  Acceleration  of  the  blood  flow  through  the  capillaries. 

(3)  Diminution  of  the  amount  of  proteins  in  the  blood- 
plasma.    ' 


THE    OUTPUT    OF    FLUID 


115 


When  a  concentrated  solution  of  salts  is  injected  into  the 
circulation,  the  osmotic  pressure  of  the  plasma  is  raised  and 


180 
170 
160 
150 

uo 

130 

1-20 

110 

100 

90 

80 

70 

CO 

:.0 

40 

30 

20 

10 


10   20   .JO    49    :,0        (JO    70    80   90   100   110   120  130   140   loO 

Fig.  10. — Curves  showing  effect  of  intravenous  injection  of  a  strong 
solution  of  glucose  on  the  arterial  blood  pressure,  on  the  volume  of  the 
circulating  blood  (as  judged  by  the  hsemoglobin  percentage),  on  the 
volume  of  the  kidney  and  on  the  secretion  of  uiine. 

there  is  at  once  a  passage  of  water  from  the  tissue  cells  into 
the  blood  stream,  in  consequence  of  the  osmotic  differences 
between  the   blood   and   cells  so   induced.      As  a  result  the 

I  2 


r 

A 

\ 

\ 

\, 

■  -h 

X 

.^ 

^ 

Art.  BP 

.   mm 

Hg 

HaemoglobiR 

L 

^»-» 

.--- 

, »-"'' 

Perce 

nt. 

i 

\ 

\           1 
«     f 

■'\ 

\ 

4 
0 

* 

\ 

m 
f 

\ 

\ 

/     1 

\ 

f    ^ 

\ 

/ 

p 

CD 

\ 

V 

o 

V 

^^ 

Kidnpv   Volume 

'-■J 

c 
.2 

o 

CD 

-^ 

^^ 



/ 

^ 

^^ 

-— 

Qrine 

~         1           i 

116  THE  FLUIDS  OF  THE  BODY 

total  volume  of  the  circulating  fluid  is  increased  by  the 
addition  to  it  of  water  derived  from  the  tissues,  i.e.,  a 
condition  of  hydrgemic  plethora  is  set  up.  The  effect  is  the 
same  as  if  a  large  bulk  of  normal  saline  fluid  had  been 
injected  into  the  circulation.  So  long  as  this  hydrsemic 
plethora  continues,  so  long  is  there  a  rise  both  in  arterial 
and  venous  pressures  and  an  increase  in  the  velocity  of  the 
circulating  blood.  The  kidney  placed  in  an  oncometer 
shows  a  great  increase  in  volume.  While  the  plethora  lasts 
there  are  mechanical  conditions  at  work  in  the  kidneys, 
i.e.,  increased  pressure,  increased  rate  of  flow,  and  diminished 
concentration  of  plasma,  all  of  which  would  concur  in  pro- 
ducing an  increased  glomerular  transudation.  "With  certain  sub- 
stances, such  as  sodium  chloride,  the  diuresis  is  co-terminous 
with  the  hydraemic  plethora ;  with  others  of  this  class,  such  as 
grape  sugar,  the  diuresis  outlasts  the  plethora,  so  that  the 
continued  increased  secretion  of  urine  leads  to  an  actual 
concentration  and  diminution  of  volume  of  the  circulating 
blood,  as  is  shown  in  the  Figure. 

If  the  kidney  be  placed  in  an  oncometer,  it  is  found  that 
the  dilatation  of  the  kidney  outlasts  the  plethora  and  comes 
to  an  end  only  with  the  cessation  of  the  increased  urinary 
flow.  Local  influences  therefore  must  be  at  work  (perhaps 
the  direct  effect  of  the  sugar  on  the  blood  vessels)  which 
lead  to  an  active  dilatation  of  the  renal  vessels  and  a  conse- 
quent rise  of  pressure  and  increased  velocity  of  the  blood  in 
the  glomeruli.  That  this  vascular  change  is  really  responsible 
for  the  increased  urinary  flow  is  shown  by  the  fact,  determined 
by  Cushny,  that  if  the  swelling  of  the  kidney  be  prevented  by 
means  of  an  adjustable  clamp  on  the  renal  artery,  no  diuresis 
is  produced :  so  long  as  the  kidney  is  kept  at  its  normal  size 
the  flow  of  urine  remains  at  the  same  rate  as  before. 

With  regard  to  the  specific  diuretics  such  as  caffeine,  the 


THE    OUTPUT    OF    FLUID  117 

question  is  not  quite  so  clear.  In  most  cases  injection  of 
caffeine  in  the  rabbit  brings  about  a  dilatation  of  the  kidney 
and  a  proportional  increase  in  the  secretion  of  urine.  But 
cases  have  been  recorded  in  which  an  increase  in  kidney 
volume  occurred  without  increase  in  urinary  flow,  or  on  the 
other  hand  an  increase  in  urinary  flow  without  any  increase 
in  the  kidney  volume,  or  even  in  the  rate  of  blood  flow 
through  the  kidney  (as  determined  by  Brodie's  method).  The 
general  rule  however  is  that  an  increased  blood  flow  is 
obtained  pari  passu  with  the  increased  urinary  flow,  and  a 
consideration  of  certain  peculiarities  in  the  renal  circulation 
must  prevent  us  from  laying  too  much  stress  on  apparent 
exceptions  to  the  rule.  To  the  blood  entering  the  kidneys  by 
the  renal  arteries  two  wajs  are  oj^en.  The  blood  may  pass 
through  the  vasa  afferentia,  through  the  glomeruli  and  tubular 
capillaries,  back  to  the  renal  vein.  On  the  other  hand,  it  may 
escape  the  glomeruli  altogether  and  pass  through  the  vasa 
recta  directly  into  the  interlobular  capillaries  and  so  into  the 
renal  veins.  It  is  a  common  experience  in  injecting  the  blood 
vessels  of  the  kidneys  post-mortem  to  find  the  renal  arteries, 
interlobular  capillaries,  and  veins  filled  to  distension  with  the 
injected  mass,  but  hardly  any  injection  in  any  of  the  glomeruli. 
One  must  assume  in  such  a  case  that  there  has  been  spasmodic 
contraction  of  the  muscular  coats  or  of  the  vasa  afferentia. 
The  blood  circulating  through  the  kidney  might  therefore  attain 
its  normal  extent  and  yet,  on  account  of  such  contraction,  no 
blood  at  all  be  flowing  through  the  filtering  apparatus,  i.e.,  the 
glomeruli.  On  the  other  hand,  a  dilatation  of  the  afferent 
vessels  and  a  slight  constriction  of  the  efferent  vessels  would 
cause  a  big  rise  of  pressure  in  the  glomerular  capillaries  and 
a  consequent  increased  transudation,  without  necessarily 
altering  to  any  marked  extent  the  total  circulation  of  blood 
through  the  whole  organ.     The  changes  in  the  afferent  and 


118  THE  FLUIDS  OF  THE  BODY 

efferent  vessels  and  the  glomeruli  are  however  beyond  our 
control  or  powers  of  observation,  so  that  it  is  impossible  to 
devise  at  the  present  time  any  crucial  experiment  which  might 
decide  the  nature  of  the  process  occurring  in  the  glomeruli. 

The  Composition  of  the  Urine. — If  the  glomerular  function 
is  that  of  mere  filtration  we  should  expect  that,  the  more 
rapidly  the  process  occurs,  the  more  nearly  would  the  urine, 
which  is  turned  out  into  the  ureters,  resemble  the  blood- 
plasma  in  composition,  reaction,  and  osmotic  pressure,  since 
the  glomerular  filtrate  hurried  through  the  tubules  would 
have  very  little  time  to  undergo  any  changes  resulting  in  its 
concentration.  If,'  on  the  other  hand,  the  diuresis  produced 
by  salt  or  sugar  solutions  is  to  be  ascribed  to  a  stimulation  of 
the  renal  epithelium,  we  should  expect  the  differences  between 
blood-plasma  and  urine  to  be  greatest  at  the  height  of  the 
diuresis,  when  the  specific  stimulant  is  present  in  the  blood 
in  largest  amounts.  The  following  experiment  shows  that, 
the  more  rapid  the  secretion  of  urine,  the  more  closely  does  its 
concentration,  as  indicated  by  its  osmotic  pressure  and  depres- 
sion of  freezing  point  (a)  ?  appi'oximate  that  of  the  blood-plasma. 
A  dog  received  40  gms.  of  dextrose  dissolved  in  40  cms.  of 
water.  The  Table  opposite  represents  the  relative  concentra- 
tions of  urine  and  blood  serum  at  different  stages  in  the 
diuresis  thereby  produced. 

A  still  nearer  approximation  of  the  concentration  of  the 
urine  to  that  of  the  plasma  was  obtained  by  Galeotti  *  in  some 
experiments,  in  which  the  modifying  influence  of  the  tubular 
epithelium  on  the  glomerular  transudate  had  been  prevented 
by  poisoning  the  animal  with  corrosive  sublimate,  which 
causes  destruction  of  the  epithelium  but  is  said  to  leave  the 
glomeruli  intact. 

-  Ardiiv.f.  {Anat.  u.)  Fhys.,  200,  1902. 


THE    OUTPUT    OF    FLUID 


119 


Since  the  glomerular  transudate  must  have  a  concentration 
approximately  identical  with  that  of  the  blood-plasma,  it 
would  be  impossible  for  a  urine  formed  by  mere  filtration 
to  have  a  concentration  less  than  that  of  the  blood-plasma. 
It  is  however  of  frequent  occurrence  that  after  copious 
potations  of  tea  or  light  beer,  urine  is  passed  with  an 
osmotic  pressure  and  a  molecular  concentration  considerably 
below  that  of  the  blood.  In  one  case  Dreser*  obtained  a  urine 
with  a  freezing  point  of  A  =  0*16°  C,  and  the  same  result  has 


Time. 

Urine. 

Rate  of  flow. 

A  of  Urine. 

A  of  blood  serum. 

11.30—12 

10  cc. 

3-3 

2-360 

•625  (at  12.0) 

From  12.0  to  12.7  injected  40  gr^ms.  dextrose  into  jugular  vein. 


12.7  —12.15 

35  cc. 

45 

1-210 

/ 

12.16—12.20 

20  cc. 

50 

0-975 

•700  (at  12.16) 

12.20—12.30 

52  cc. 

52 

0-835 

12.30—12.40 

45  cc. 

45 

0-825 

-700  (at  12.30) 

12.40—12.50 

22  cc. 

22 

0-830 

-675  (at  12.4^7 
-675  (at  12.50) 

been  obtained  on  one  or  two  occasions  when  the  diuresis  has 
been  produced  by  the  administration  of  caffeine.  If  we  assume 
that  this  hypotonic  fluid  is  formed  by  the  glomeruli,  we 
must  at  once  give  up  any  idea  of  the  process  in  these  struc- 
tures being  essentially  one  of  filtration.  In  dealing  however 
with  the  functions  of  the  tubules,  we  shall  see  that  there  is 
definite  evidence  of  the  possession  by  their  epithelium  of  a 
secretory  power  for  water  as  well  as  for  solid  constituents. 
The  fine  adaptation  of  the  kidney  to  slight  changes  in  the 


^  Schmiedeberg's  Archiv,  XXIX.  303,  1892. 


120  THE  FLUIDS  OF  THE  BODY 

composition  of  the  blood  is  apparently  an  endowment  of  the 
tubular  epithelium,  and  in  those  cases,  where  large  quantities 
of  hypotonic  urine  are  passed,  there  is  not  at  any  time  any 
appreciable  change  either  in  the  composition  of  the  blood  or  in 
its  total  volume.  Water  is  absorbed  from  the  alimentary  canal 
and  is  almost  immediately  excreted  by  the  kidneys.  When 
we  attem^Dt  to  produce  the  same  effect  by  infusion  of  large 
quantities  of  water  or  hypotonic  solutions  into  the  blood 
stream,  we  get  a  flow  of  urine  apparently  determined  entirely 
by  the  circulation  through  the  kidney  and  having  a  con- 
centration not  inferior  to  that  of  the  blood.  The  passage  of 
hypotonic  urine  can  be  ascribed  to  a  modification  of  the 
glomerular  transudate  as  it  passes  through  the  tubules,  a 
modification  due  partly  to  the  absorption  of  salts  from 
the  fluid,  partly,  perhaps  chiefly,  to  a  secretion  of  water  or 
extremely  dilute  salt  solutions  by  the  cells  of  the  tubules 
themselves. 

Certain  other  observations  accord  with  our  hypothesis  that  in  Bowman's 
capsule  a  fluid  is  transuded  having  the  same  molecular  concentration  as 
"blood-plasma,  and  therefore  considerably  less  concentrated  than  normal 
^^iine.  Eibbert  succeeded  in  extirpating  the  whole  of  the  medullary 
portion  of  the  kidney  in  the  rabbit,  leaving  the  cortex  intact,  and  found 
in  this  case  that  during  the  survival  of  the  animal  the  urine  that  was 
passed  was  much  more  dilute  than  normal.  In  cases  too  where  there  is 
destraction  of  the  tubular  epithelium,  while  the  glomeruli  remain  intact, 
either  in  consequence  of  disease  or,  as  in  Galeotti's  experiments,  as  a 
result  of  poisons,  we  are  accustomed  to  obtain  a  dilute  copious  urine,  and 
the  continual  2)assage  of  such  urine  is  in  man  regarded  as  a  sign  of  one 
form  of  renal  disease. 

The  experimental  facts  which  we  have  passed  in  review  do 
not  therefore  negative  the  view  that  the  glomerular  epithelium 
j)lays  the  part  of  a  passive  filter  in  the  formation  of  urine, 
and  that  the  energy  of  the  process  by  which  urine  is  produced 
in  Bowman's  capsule  is  entirely  furnished  by  the  heart  in 
producing  the  blood  flow  through,  and  the  blood  pressure  in, 


THE    OUTPUT    OF    FLUID  121 

the  glomerular  capillaries.  Before  coming  to  any  conclusion 
however  as  to  the  importance  to  be  ascribed  to  this  function 
in  the  formation  of  urine,  we  must  turn  our  attentions  to 
the  functions  of  the  greater  part  of  the  kidneys,  namely,  the 
tubules. 

Functions  of  the  Kenal  Tubules. 

Whatever  the  nature  of  the  glomerular  activity  it  is  evident 
that  the  multiform  epithelium  of  the  tubules  may  alter  the 
glomular  transudate,  either  by  the  absorption  or  by  the 
secretion  of  water  or  soUd  constituents.  We  may  deal  with 
the  evidence  for  the  occurrence  of  these  two  processes 
separately. 

Evidence  for  Secretion  hy  the  Urinary  Tubules. — Although 
it  is  impossible  to  collect  the  secretion  of  the  glomeruli  apart 
from  that  of  the  tubules,  the  arrangement  of  the  blood  vessels 
in  certain  animals  enables  us  to  influence  separately  the  circu- 
lation to  these  two  parts  of  the  kidney.  The  amphibian  kidney 
receives  a  blood  supply  from  two  sources.  A  number  of  renal 
arteries  leaving  the  aorta  pass  into  the  kidney  and  supply 
the  whole  of  the  glomeruli,  the  vasa  efferentia  from  which 
pass,  as  in  the  mammalian  kidney,  into  the  intertubular 
capillaries.  These  are  also  supplied  with  blood  of  venous 
character  by  the  renal  portal  vein.  If  the  whole  of  the  renal 
arteries  be  divided  or  ligatured,  the  glomeruli,  as  was  shown 
by  Nussbaum,  are  entirely  cut  out  of  the  circulation,  though 
the  tubules  continue  to  receive  venous  blood  through  the  renal 
portal  vein. 

Nussbaum  stated  that  the  ligature  of  all  the  renal  arteries 
caused  cessation  of  the  urinary  secretion,  which  could  be  re- 
induced  by  injection  of  urea.  He  therefore  concluded  that 
urea  with  water  was  secreted  by  the  tubules,  whereas  jDeptone, 
sugar,   and  haemoglobin   were  turned   out  by  the  glomeruli. 


122  THE  FLUIDS  OF  THE  BODY 

Beddard  *  showed  however  that  these  results  of  Nussbaum's 
must  have  been  due  to  the  fact  that  he  had  not  obstructed 
the  whole  of  the  renal  arteries.  One  or  tw^o  of  these  small 
vessels  will  suffice  to  supply  blood  to  a  considerable  area  of 
the  glomeruli  of  the  kidney.  He  found  that,  after  complete 
obstruction  of  the  arteries,  no  urinary  flow  could  be  induced 
even  with  subcutaneous  injection  of  urea.  But  the  cutting- 
off  of  the  arterial  blood  sup23ly  from  the  tubules  caused  a 
rapid  destruction  of  the  tubular  epithelium,  so  that  one  could 
not  take  the  result  of  the  experiment  as  negativing  the  pos- 
sibility of  this  epithelium  having,  when  in  a  normal  state  of 
nutrition,  some  amount  of  secretory  power.  He  therefore 
carried  out  with  Bainbridge  t  another  series  of  experiments 
of  the  same  description,  in  which  the  frogs,  after  ligature 
of  the  renal  arteries,  were  kept  in  an  atmosphere  of  pure 
oxygen.  Under  these  circumstances  sufficient  oxygen  diffused 
into  the  blood  of  the  renal  portal  vein  to  maintain  an  adequate 
supply  of  oxygen  to  the  tubules.  No  desquamation  of  the 
epithelium  resulted,  and  injection  of  urea  produced  a  small 
flow  of  urine  even  when,  by  subsequent  injection  of  the  blood 
vessels,  it  was  proved  that  every  glomerulus  had  been  cut  out 
of  the  circulation.  Similar  results  have  been  obtained  by 
Brodie  and  Cullis  §  in  certain  experiments  in  which  oxyge- 
nated Einger's  fluid  was  led  through  the  surviving  kidney  of 
the  frog.  A  small  flow  of  urine  was  obtained,  especially  after 
urea  or  potassium  nitrate  had  been  added  to  the  fluid.  The 
quantities  of  urine  obtained  in  these  two  sets  of  experiments 
were  too  small  to  admit  of  a  proper  analysis  or  of  a  com- 
parison of  their  molecular  concentration  with  that  of  the 
blood  serum  of  the  animal.  "^ 

*  Journ.  ofPhijsiol,  XXVHI.,  20,  1902. 

f  Biochemical  Journal,  I.,  255,  1906. 

i^  Journ.  of  riiysioL,  XXXIV.,  224,  1906, 


THE    OUTPUT    OF    FLUID  123 

The  definite  evidence  thus  afforded  of  the  possession  of  a 
secretory  function  by  a  certain  portion  at  any  rate  of  the 
tubules  is  borne  out  by  a  histological  examination  of  these 
structures  under  various  conditions  of  activity.  In  the  cells 
of  the  convoluted  tubules  various  kinds  of  granules  and  of 
vacuoles  may  be  distinguished.  Gurwitsch  divides  these 
vacuoles  into  three  classes  : — 

(1)  Large  granules  staining  densely  with  osmic  acid,  and 
probably  rich  in  lecithin  ; 

(2)  Smaller  very  numerous  granules  consisting  of  some  form 
of  protein  material ; 

(3)  Large  vacuoles  lying  close  to  the  free  margin  of  the  cells 
whose  contents  do  not  undergo  coagulation  with  the  ordinary 
fixing  reagents,  and  therefore  are  free  from  protein,  fat,  or 
mucin.  These  vacuoles  are  especially  marked  in  kidneys, 
which  are  secreting  at  a  great  rate  in  consequence  of  the 
injection  of  saline  diuretics  or  of  large  quantities  of  normal 
salt  solution.  They  are  probably  to  be  regarded  as  excretory 
vacuoles  and  as  representing  water  or  saline  fluids  which  have 
been  collected  by  the  cells  and  are  being  passed  on  by  them  to 
the  lumen  of  the  tubules. 

As  a  rule  it  is  impossible  to  trace  any  definite  constituent  of 
the  urine  on  its  way  through  the  cells  of  the  tubules.  If 
however  a  solution  of  uric  acid  in  piperazin  be  injected  intra- 
venously into  a  rabbit,  the  kidneys,  taken  20  to  60  minutes 
after  the  injection,  present  tubules  full  of  uric  acid  concretions. 
In  the  medullary  portion  of  the  kidney  this  uric  acid  pre- 
cipitate is  confined  to  the  lumen  of  the  tubules,  but  in  the 
convoluted  tubules  granules  of  uric  acid  are  to  be  found  in  the 
epithelial  cells,  especially  towards  their  inner  borders.  Since 
these  cells  are  able  to  excrete  uric  acid  when  present  in 
abnormal  quantities  in  the  blood,  it  is  a  reasonable  assump- 
tion that  they  also  undertake  the  secretion  of  this  substance 


124  THE  FLUIDS  OF  THE  BODY 

under  normal  conditions.  Certain  observers  have  in  fact 
described  the  presence  of  urate  granules  in  the  cells  of  the 
convoluted  tubules  of  the  bird's  kidney. 

Although  the  larger  number  of  the  urinary  constituents 
must  escape  detection  on  their  way  through  the  cells,  we  can 
throw  some  light  on  the  excretory  functions  of  the  kidney  by 
studying  the  mechanism  by  which  it  excretes  certain  dye- 
stuffs,  such  as  sulphindigotate  of  soda  or  indigo  carmine. 
If  the  indigo  be  injected  into  the  veins,  after  section  of  the 
cord  to  stop  the  urinary  flow,  and  the  animal  be  killed  half 
an  hour  later  and  the  kidneys  fixed  with  absolute  alcohol, 
although  no  urine  has  been  obtained  in  the  interval  the 
kidneys  are  found  to  be  of  a  bright  blue  colour.  On  cutting 
into  the  kidneys  the  colour  is  seen  to  be  confined  to  the 
cortex,  and  on  making  microscopic  sections  granules  of  the 
pigment  are  found  within  the  lumen  of  the  convoluted  tubules 
and  also  in  the  cells  lining  these  tubules.  It  has  been 
suggested  by  several  physiologists  that  the  appearances  after 
the  injection  of  indigo  are  due,  not  to  the  secretion,  but  to  the 
absorption  of  water  in  the  convoluted  tubules.  A  certain 
amount  of  the  dye-stuff  is  thus  rendered  visible  by  becoming 
more  concentrated,  and  is  precipitated  in  a  granular  form  as 
soon  as  the  salt  concentration  of  the  fluid  reaches  a  certain 
height.  The  fact  that  these  appearances  are  wanting  after  the 
injection  of  ordinary  carmine,  which  stains  the  glomeruU  as 
well  as  the  tubules,  combined  with  the  histological  facts  men- 
tioned in  the  last  paragraph,  render  this  a  somewhat  forced 
explanation ;  and  we  must  take  the  results  of  the  injection  of 
indigo  carmine  as  telling  rather  in  favour  of  a  secretory  than  of 
an  absorptive  function  on  the  part  of  the  convoluted  tubules. 

The  question  as  to  the  secretory  activity  of  the  kidney  can 
be  attacked  from  another  side.  The  glomerular  filtrate  can 
only  contain  those  crystalloids  of  the  blood  which  are  diffusible 


THE    OUTPUT    OF    FLUID  125 

and  are  not  closely  combined  with  its  colloidal  constituents. 
Lowi  has  shown  that  in  this  connection  a  contrast  is  to  be 
drawn  between  the  behaviour  of  substances  such  as  urea  or 
sodium  chloride  and  certain  other  constituents  of  the  blood 
such  as  phosphates  or  sugar.  Any  increase  in  the  rate  at 
which  the  glomerular  secretion  takes  place  must  cause  a  corre- 
sponding increase  in  the  total  amount  of  the  solid  diffusible 
constituents  of  the  blood-plasma  which  are  turned  out  within 
a  given  time.  Thus  every  diuresis  increases  the  total  output 
of  chlorides  and  of  urea.  It  is  worthy  of  note  that  under 
normal  circumstances  a  diuresis,  caused  for  example  by 
drinking  large  quantities  of  water,  does  not  increase  tbe  total 
output  of  phosphates  in  a  given  time,  nor  does  it  increase  the 
very  small  amount  of  sugar  which  is  normally  excreted  by  the 
kidneys.  If  however  phosphates  be  present  in  the  blood  in 
an  unattached  condition,  as,  for  instance,  in  consequence  of 
previous  injection  of  sodium  phosphate  into  the  blood,  then 
any  diuresis  increases  the  amount  of  phosphates  put  out  in  a 
given  time.  The  same  thing  holds  for  sugar.  If  an  excess  of 
free  uncombined  sugar  be  present  in  the  blood  either  in  con- 
sequence of  intravenous  injection  of  this  substance  or  as  a 
result  of  previous  extirpation  of  the  pancreas,  any  form  of 
diuresis  will  increase  the  rate  at  which  it  is  turned  out  by  the 
kidneys.  Lowi  concludes  therefore  that  phosphates,  which 
must  be  present  in  minimal  quantities  in  the  glomerular 
transudate,  are  for  the  most  part  secreted  by  the  activity  of 
the  cells  of  the  convoluted  tubules.  Under  normal  conditions, 
e.g.,  as  after  administration  of  phloridzin,  the  cells  of  the 
kidneys  can  be  excited  to  a  similar  activity  with  regard  to 
sugar.  After  phloridzin  injection  the  urine  contains  consider- 
able quantities  of  sugar,  but  the  rate  at  which  the  sugar  is 
secreted  is  not  affected  in  any  way  by  raising  the  rate  of 
urinary  secretion  {e.g.,  by  the  injection  of  such  substances  as 


126  THE  FLUIDS  OF  THE  BODY 

sodium  sulphate,  which  increases  the  rapidity  of  the  glomerular 
process  of  transudation). 

Evklence  of  Absorption  by  the  Renal  Tubules. — The  experi- 
ments of  Eibbert,  mentioned  above,  in  which  removal  of  the 
medullary  portion  of  the  kidney  led  to  the  formation  of  an 
increased  quantity  of  more  watery  urine,  points  to  the  posses- 
sion by  the  tubules  of  a  power  of  absorbing  water.  We  have 
other  evidence  that  this  power  of  resorption  is  not  confined  to 
water,  but  may  affect  also  the  dissolved  constituents  of  the 
glomerular  transudate.  It  was  pointed  out  by  Meyer  that,  if 
two  salts  such  as  sodium  sulphate  and  sodium  chloride  were 
present  at  the  same  time  in  the  glomerular  transudate,  any 
process  of  resorption  should  affect  chiefly  the  more  diftusible 
salt,  namely,  sodium  chloride.  Such  a  differential  resorption 
would  account  for  the  much  greater  diuretic  power  of  sodium 
sulphate  as  compared  with  sodium  chloride.  In  certain 
experiments  Cushny  *  produced  a  diuresis  by  the  injection  of 
equal  parts  of  equivalent  NaCl  and  Na2S04  solutions  into  the 
veins  of  a  rabbit.  An  increased  flow  of  urine  was  produced, 
which  lasted  two-and-a-half  hours.  The  chlorides  of  the  urine 
rose  with  the  diuresis  and  reached  their  maximum  at  the 
height  of  the  urinary  flow.  They  then  sank,  and  in  some 
experiments  had  practically  disappeared  altogether  from  the 
urine  towards  the  end  of  the  observation.  The  concentration 
of  the  sulphates  however  continued  to  rise  in  the  urine  to 
the  end  of  the  experiment.  Thus,  in  the  first  of  two  identical 
experiments,  when  the  rabbit  was  killed  at  the  height  of  the 
diuresis,  the  serum  contained  '547  per  cent,  chlorine  and  '259 
per  cent,  sulphate,  while  the  urine  contained  '372  per  cent, 
chlorine  and  '546  per  cent,  sulphate.  In  the  second,  in  which 
the  rabbit  was  killed  when  the  rate  of  the  urinary  flow  had 

-  Journ.  of  Physiol.,  XXVII.,  427,  1901. 


THE    OUTPUT    OF    FLUID 


127 


considerably  diminished,  the  serum  contained  '493  per  cent, 
chlorine  and  '191  per  cent,  sulphate,  while  the  urine  con- 
tained '094  per  cent,  chlorine  and  2*0  per  cent,  sulphate. 
These   results   are   illustrated  by  the  accompanying  Figure 


\ 

\ 

i 

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V 
Y 

Y 

\ 

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A 

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1   / 

*J 

.\ 

t 

/ 

\ 

V  \ 

j 

/ 

\ 

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ll 

/ 

A 

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i 

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s\ 

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i 

/ 

>^ 

V  ^ 

^ 

1 

1 

\ 

x 

\, 

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V 

s. 

s 

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f 

V 

-^K — 

\ 

"^ 

Lh^ 

N 

•-> 

>- 

..- 

— -. 

15     30     45     60     75     90     105    180    135 

Fig.  11. — Curves  showing  excretion  of  urine  (lieavy  unbroken  line),  of 

/^O  \  /CI 

sulphate  equivalents  \^^  light  line),  and  of  CI  equivalents  {  ot;^.  broken 

line),  after  injection  of  50  cc.  of  a  solution  containing  l'77o  gr.  CI  and 
4*8  gr.  SO4  per  100  cc.  The  heavy  line  along  the  base  shows  the  dui-ation 
of  the  injection. 

(Fig.  11),  showing  the  excretion  of  sulphates  and  chlorides 
in  a  rabbit  after  injection  of  50  cc.  of  a  solution  of  the 
sulphate  and  chloride  of  sodium. 

The  difference  between  the  two  salts  can  be  made  still  more 
striking  if  the  process  of  resorption  be  augmented  by  increasing 
the  pressure  within  the  tubules  by  partial  obstruction  of  one 


128 


THE    FLUIDS    OF    THE    BODY 


ureter.  Thus  in  one  experiment,  where  diuresis  was  produced 
by  the  injection  of  30  cc.  of  a  solution  containing  5*85  per  cent. 
NaCl  +  14*2  per  cent.  Na2S04,  the  right  ureter  was  partially 
clamped  so  as  to  make  the  right  kidney  secrete  against  a 
pressure  of  30  mm.  Hg.  The  following  results  were 
obtained : — 


4.37  till  4.47 


Left  kidney 
Eight  kidney  .  . 
Difference  (absorption) 


Urine  cc. 

Cl.g. 

24 

0-0809 

8 

0-0142 

16 

0-0677 

S04g. 


0-1080 
0-0667 
0-0413 


We  must  conclude  that  the  tubular  epithelium  possesses  the 
power  of  modifying  the  glomerular  transudate,  not  only  by 
the  absorption  of  water,  but  also  by  the  absorption  of  dissolved 
constituents,  and  that  the  relative  permeability  of  the  cells  to 
these  constituents  is  at  any  rate  one  factor  in  determining  the 
substances  absorbed.  It  is  not  however  the  only  factor. 
The  function  of  the  kidney  is  to  preserve  the  normal  constitu- 
tion of  the  body  fluids  by  turning  out  those  substances  which 
are  abnormal  or  present  in  too  great  an  amount.  The 
behaviour  of  the  tubule  cells  with  regard  to  any  given  sub- 
stance will  therefore  depend  to  a  certain  extent  on  the 
previous  nutritive  history  of  the  body.  If  for  instance  the 
body  is  overloaded  with  sodium  chloride,  in  consequence  of 
the  administration  of  large  quantities  of  this  salt  to  the 
animal  during  the  few  days  preceding  the  experiment,  the 
salt  itself  becomes  an  abnormal  constituent,  and  the  kidney 
secretes  a  urine  far  richer  in  sodium  chloride  than  is  the 
blood-plasma.  Moreover  when  diuresis  is  produced  in  such 
an  animal  by  the  injection  of  equivalent  quantities  of  sodium 
chloride  and  sodium  sulphate,  there  is  no  diminution  of  the 


THE    OUTPUT    OF    FLUID  129 

NaCl  in  the  urine  towards  the  end  of  the  diuresis,  but  its  per- 
centage rises  steadily  as  the  rate  of  urinary  flow  diminishes. 
On  the  other  hand  a  total  deprivation  of  sodium  chloride 
extending  over  several  days,  although  not  altering  to  any 
large  extent  the  percentage  amount  of  this  salt  in  the  blood- 
plasma,  leads  to  a  total  disappearance  of  the  salt  from  the 
urine,  the  whole  of  the  sodium  chloride  present  in  the 
glomerular  transudate  being  absorbed  on  its  way  through 
the  urinary  tubules. 

It  has  been  suggested  that  the  effects  of  certain  diuretics  on 
the  kidney,  such  as  caffeine,  diuretine,  or  theocine,  may  be 
largely  conditioned,  not  so  much  by  their  influence  on  the 
glomerular  circulation,  as  by  a  paralytic  effect  on  the  absorp- 
tive functions  of  the  tubules.  According  to  Loewi  *  on  injec- 
tion of  caffeine  or  diuretine,  the  increase  of  total  amount 
of  urine  is  not  accompanied  by  any  diminution  in  the  per- 
centage amount  of  NaCl.  Perhaps  however  the  strongest 
evidence  in  this  direction  is  afforded  by  an  experiment  of 
Pototzky.f  A  rabbit  had  been  fed  on  a  diet  almost  totally 
devoid  of  chlorides  and  was  therefore  excreting  a  urine  con- 
taining only  0'08  j)er  cent.  NaCl.  Under  the  influence  of 
diuretine  the  urine  was  increased  and  the  concentration  of  the 
NaCl  rose  to  "64  per  cent.  The  same  increase  in  the  per- 
centage amount  of  sodium  chloride  in  the  urine  has  also  been 
observed  after  the  injection  of  theocine,  which  has  therefore 
been  specially  recommended  as  a  diuretic  in  cases  of  drojDsy, 
where  a  diminution  of  the  salt  content  of  the  body  is  a 
valuable  means  for  the  diminution  of  the  dropsical  fluid 
present  in  the  tissue  spaces. 

What  conclusions  can  we  draw  from  this  mass  of  experi- 
mental data  as  to  the  functions  of  the  kidney  as  a  whole,  and 

-  Schmiedeberg's  Archiv,  XL VIII.,  416,  1902. 
t  Pfluger's  Archiv,  XCI.,  588,  1903 

F.B.  K 


130  THE  FLUIDS  OF  THE  BODY 

as  to  the  part  played  by  its  various  constituent  elements  in 
the  secretion  of  urine  ?  The  amazing  adaptabihty  of  its 
functions  to  the  needs  of  the  organism  has  been  abundantly 
illustrated  in  the  facts  with  which  we  have  dealt.  Its  ordinary 
activity  is  determined  by  the  production,  as  a  result  of  the 
normal  processes  of  metabolism,  of  soluble  non-volatile  sub- 
stances in  every  cell  of  the  body.  These  substances,  together 
with  the  excess  of  water  taken  in  with  the  food  above  that 
lost  by  respiration  and  cutaneous  transpiration,  are  turned 
out  by  the  kidney  as  urine.  The  activity  of  this  organ  must 
therefore  be  aroused  in  the  first  place  by  chemical  stimuli. 
It  must  react  to  the  slightest  deviation  from  normal  of  the 
blood  composition,  by  excreting  water  or  dissolved  substances. 
This  delicate  sensibility  is  displayed  in  two  directions : 

(1)  Under  the  influence  of  certain  substances,  such  as  urea, 
uric  acid  or  water,  the  cells  of  the  convoluted  tubules  take  up 
the  substance,  which  is  in  excess,  from  the  surrounding 
lymph  and  accumulate  it  in  vacuoles,  which  are  discharged 
on  the  inner  surface  of  the  cells  into  the  lumen  of  the 
tubules. 

(2)  Besides  this  specific  secretory  activity  of  the  cells  of  the 
convoluted  tubules,  the  tubules  as  a  whole  are  endowed  with 
the  power  of  absorbing  both  water  and  dissolved  substances 
from  the  fluid  in  their  lumen.  Whether  this  absorptive 
power  is  limited  to  the  cells  of  Henle's  loop,  as  was  first 
suggested  by  Ludwig,  or  occurs  coincidently  with  secretion  in 
the  cells  of  the  convoluted  tubules,  as  might  be  imagined  from 
the  close  analogy  between  the  structure  of  these  cells  and  that 
of  the  intestinal  epithelium,  we  have  not  suflicient  evidence  to 
decide.  We  do  know  however  that  the  quality  of  the  absorption 
is  strictly  regulated  according  to  the  needs  of  the  organism,  so 
that  the  constituents,  which  are  precious,  are  reabsorbed  for 
service  in  the  body,  while  those  which  are  in  excess  or  are  of 


THE    OUTPUT    OF    FLUID  131 

no  value  to  the  organism,  are  allowed  to  pass  out  into  the 
ureters.  The  process  of  resorption  is  indeed,  as  is  shown  by 
Cushny's  experiments,  largely  dependent  on  the  physical 
qualities  of  the  substances  undergoing  absorption,  and  especi- 
ally on  the  permeability  of  the  renal  cells  to  these  substances. 
The  physical  conditions  are  however  subordinated  to  the 
physiological,  so  that  a  salt  so  diffusible  as  potassium  iodide 
is  left  in  the  fluid,  while  sodium  chloride  may  be  reabsorbed 
in  large  quantities. 

The  necessity  for  the  endowment  of  the  tubular  epithelium 
with  a  resorptive  as  well  as  a  secretory  function  is  determined 
by  the  presence  at  the  beginning  of  the  tubule  of  a  mechanism 
— the  glomerulus,  which  is  in  all  probability  devoid  of  the  fine 
selective  power  or  chemical  sensibility  possessed  by  the  cells 
of  the  convoluted  tubules.  The  production  of  urine  by  the 
glomerulus  is  apparently  regulated  entirely  by  the  pressure 
and  velocity  of  the  blood  through  its  capillaries  and  by  the 
colloid  content  of  the  blood-plasma.  We  may  assume  that 
in  Bowman's  capsule  there  is,  under  normal  conditions,  a 
constant  production  of  a  fluid  free  from  protein  but  having 
the  same  crystalloid  concentration  as  the  blood-plasma. 
With  any  rise  of  general  blood  pressure,  the  amount  of  this 
transudate  is  increased ;  with  any  fall  it  is  diminished.  The 
small  qualitative  changes  which  are  constaritly  occurring  in 
the  blood,  as  the  result  of  the  taking  of  food  or  the  activity  of 
different  organs,  probably  produce  but  little  effect  on  the 
amount  of  glomerular  fluid.  Only  indirectly,  as  the  result  of 
their  influence  on  the  general  blood  pressure,  or  possibly  in 
consequence  of  the  production  of  substances  having  a  vaso- 
dilator effect  on  the  renal  vessels,  will  the  amount  of  the  urine 
turned  out  by  the  glomeruli  be  affected.  These  structures 
therefore  have  the  two-fold  function  of  regulating  the  total 
amount  of  circulating  fluid  and  of    providing  an  indifferent 

K  2 


132  THE  FLUIDS  OF  THE  BODY 

fluid,  which  will,  so  to  speak,  flush  the  kidney  tubules,  and 
carry  down  any  constituents  excreted  in  a  concentrated  form 
by  the  cells  of  these  tubules. 

The  constant  production  of  a  glomerular  transudate  might 
result,  especially  in  terrestrial  animals,  in  the  loss  to  the 
organism  of  water,  or,  under  certain  nutritive  conditions, 
of  indispensable  constituents  of  the  serum,  such  as  sodium 
chloride,  in  amounts  which  could  not  be  made  good  at  the 
expense  of  the  food.  It  is  for  this  reason  that  an  absorptive 
mechanism,  sensitive  to  and  reflecting  the  nutritive  condition 
of  the  whole  body,  especially  as  concerns  water  and  salts, 
is  needed  in  the  tubules.  As  the  result  of  the  complementary 
processes  of  absorption  and  secretion  in  the  tubules,  the 
unchanging  glomerular  filtrate  undergoes  great  modifica- 
tions in  its  passage  towards  the  ureter.  It  receives  urea, 
uric  acid,  phosphates,  and  under  certain  conditions,  water, 
from  the  cells  of  the  convoluted  tubules.  It  gives  up  salts, 
especially  sodium  chloride,  and  generally  water  to  the  same 
or  other  cells  of  the  tubules.  So  that  finally,  instead  of 
a  fluid  isotonic  with  the  blood  and  containing  only  about 
•1  per  cent,  urea,  we  have  a  fluid  of  deep  yellow  colour,  with  a 
molecular  concentration  four  or  six  times  greater  than  that  of 
the  blood,  and  containing   between  2  and  3  per  cent.  urea. 

We  have  at  the  present  time  no  means  of  judging  the  relative 
amounts  of  fluid  furnished  respectively  by  the  glomeruli  and 
tbe  tubules  to  the  fully  formed  urine.  It  is  probable  that, 
under  ordinary  circumstances,  the  processes  of  secretion  and 
absorption  of  fluid  go  on  pari  passu  in  the  urinary  tubules 
just  as  they  do  in  the  mucous  membrane  of  the  small  intes- 
tine. The  demonstration  of  secretory  powers  in  the  cells  of 
the  convoluted  tubules  relieves  us  from  the  necessity  of 
the  assumption,  made  by  Ludwig,  as  to  the  quantity  of 
fluid   normally  turned  out  through  the  glomeruli.      On  the 


THE    OUTPUT    OF    FLUID  133 

hypothesis  that  the  sole  function  of  the  tubules  was  one  of 
absorption,  and  that  all  the  urinary  constituents  were 
derived  from  the  glomerular  transudate,  30  litres  of  fluid 
would  have  to  be  filtered  through  the  glomeruli,  in  order  to 
excrete  the  30  grras.  urea,  which  is  the  daily  output  of  a 
man.  Of  these  30  litres,  28  litres  would  have  to  be  reabsorbed 
in  the  tubules.  Since  the  amount  of  blood  flowing  through 
the  two  kidneys  in  a  man  probably  varies  between  1,600  and 
1,800  litres  in  the  24  hours,  there  would  be  no  difficulty  in  the 
production  of  such  an  amount  as  30  litres,  which  would  only 
represent  a  concentration  in  the  blood  in  its  passage  through 
the  glomeruli  of  under  2  per  cent.  The  secretion  and 
reabsorption  of  such  large  quantities  of  fluid  seems,  however, 
a  clumsy  way  of  arriving  at  a  urine,  whose  composition  should 
be  adapted  to  the  needs  of  the  animal,  and,  as  we  have  seen, 
the  occurrence  of  an  actual  secretion  of  urea  by  the  cells  of 
the  tubules  takes  away  the  necessity  of  assuming  any  such 
wasteful  proceeding.  It  is  probable  that  the  actual  amount 
of  the  glomerular  filtrate  in  the  24  hours  may  not  exceed  to 
any  large  extent  the  actual  amount  of  urine  formed  by  the 
whole  kidney  in  this  time. 


LECTUEE  VII 

THE  FLUID  BALANCE  OF  THE  BODY 

Under  normal  circumstances  the  various  mechanisms  that 
we  have  discussed  in  the  preceding  lectures  work  together  for 
the  maintenance  of  an  average  quantity  and  composition  of 
the  internal  media  of  the  body.  Not,  however,  constancy  of 
amount  and  composition.  Constancy  of  any  bodily  condition 
is  unattainable  in  the  presence  of  the  varying  conditions  of 
our  environment,  and  is  indeed  not  compatible  with  our  con- 
ception of  life.  Not  only  must  there  be  deviations  from  the 
average  in  respect  to  the  total  volume  and  molecular  concen- 
tration of  the  fluid  of  the  body,  including  in  this  term  the 
blood,  lymph,  and  tissue  fluids,  but  we  may  expect  also  to 
find  variations  in  the  distribution  of  these  fluids,  any  one  of 
them  being  increased  or  diminished  at  the  expense  of  the  others. 

In  order  to  get  some  idea  of  the  interplay  of  the  mechan- 
isms concerned  in  the  regulation  of  the  body  fluids,  we 
may  deal  first  with  the  manner  in  which  the  organism  reacts 
to  changes  artificially  induced  in  the  total  quantity  of  its 
fluid  :  changes  greater,  as  a  rule,  than  those  occurring  under 
normal  circumstances,  but  on  that  very  account  presenting 
greater  facilities  for  study  and  analysis.  We  can  bring  about 
such  changes  in  the  total  fluid  by  adding  to  or  abstracting 
from  the  circulating  blood,  and  thus  study  the  reaction  of  the 
organism  to  plethora  or  to  anaemia. 

Plethora. 

A  large  increase  in  the  volume  of  the  circulating  blood 
may  be  produced  by  the  introduction  of  200  or  300  cc.  of 


THE  FLUID  BALANCE  OF  THE  BODY  135 

defibrinated  blood  from  a  dog  into  the  veins  of  another  animal 
of  the  same  species.  No  evil  effects  follow  such  injection 
unless  the  volume  of  the  blood  introduced  is  very  large  in 
comparison  with  the  total  volume  of  the  circulating  blood  in 
the  animal  receiving  the  injection.  There  is  however  a 
reaction  on  the  part  of  the  animal  to  the  injection,  which 
affects  the  mechanical  conditions  of  the  circulation,  and 
secondarily  the  lymph  production  and  the  output  of  fluid,  as 
well  as  the  metabolism  of  the  body  as  a  whole. 

The  first  effect  of  the  injection,  if  into  a  vein,  is  to 
increase  the  diastolic  filling  of  the  heart  and  its  output  into 
the  arterial  system.  On  this  account  the  arterial  pressure 
rises.  The  whole  mechanism  of  nervous  vascular  control  is 
however  directed  towards  the  maintenance  of  normal  arterial 
pressure,  and  by  this  means  a  constant  flow  of  blood  through 
the  vessels  of  the  brain.  A  rise  of  arterial  pressure  induced 
by  increased  filling  of  the  heart  brings  about  a  reflex  dilata- 
tion of  the  arterioles  and  therefore  a  difference  in  the  distri- 
bution of  pressure  within  the  vascular  system.  The  arterial 
pressure  is  thus  maintained  at  a  height  differing  but  little 
from  that  of  the  normal  pressure,  while  the  venous  pressure 
rises  and  the  greater  quantity  of  the  injected  fluid  is  accom- 
modated in  the  big  veins,  whose  capacity  is  largely  increased 
by  this  rise  of  pressure.  The  increased  venous  pressure 
involves  increased  diastolic  filling  of  the  heart.  The  output 
of  this  organ  is  therefore  increased.  Since  the  arterial  pres- 
sure is  rather  above  than  below  normal,  the  work  done  by 
the  heart  at  each  beat  must  be  also  increased. 

The  resistance  in  the  arterioles  being  diminished,  the 
output  from  the  arteries  is  increased  in  direct  proportion  to 
the  increased  output  from  the  heart,  i.e.,  there  is  a  large  rise  in 
the  velocity  of  the  blood  through  both  the  arterial  and  the 
capillary  systems.     In  the  dilatation  of  the  big  veins,  which 


136  THE  FLUIDS  OF  THE  BODY 

enables  them  to  accommodate  the  greater  part  of  the  excess 
of  fluid  in  the  vascular  system,  an  important  part  is  played 
by  the  liver  which,  in  spite  of  its  apparent  rigidity,  is 
extremely  distensible.  An  enormous  swelling  of  this  organ 
may  be  produced  by  connecting  the  inferior  vena  cava  with  a 
long  tube,  so  that  the  liver  vessels  can  be  injected  backwards 
at  a  pressure  of  about  double  the  normal,  the  portal  vein 
of  course  being  ligatured.  After  the  production  of  plethora, 
while  the  greater  part  of  the  injected  fluid  is  still  in  the 
vascular  system,  the  liver  increases  very  greatly  in  size,  and 
it  has  been  suggested  that  we  may  regard  the  liver  to  some 
extent  as  a  safety  cistern,  as  an  organ  which  can  take  up  blood 
in  its  meshes  when  there  is  any  rise  of  pressure  on  the  venous 
side  of  the  heart,  so  that  the  latter  organ  is  saved  from  the 
consequences  of  over-distension  during  diastole  and  therefore 
from  overstrain  and  possible  failure. 

The  fluid  that  has  been  introduced  does  not  long  remain 
in  the  blood  vessels.  If  a  cannula  be  inserted  into  the 
thoracic  duct,  plethora  is  found  to  be  associated  with  a  large 
increase  in  the  lymph  flow,  and  this  increase  may  be  taken 
as  representing  an  increased  transudation  in  the  abdominal 
organs  into  the  tissue- spaces,  and  through  them  into  the 
lymphatics.  There  is  in  fact,  as  a  result  of  the  rise  of 
capillary  pressures,  an  increased  leakage  of  the  fluid  con- 
stituents of  the  blood-plasma,  which  is  especially  marked  in 
the  abdominal  viscera.  Evidence  of  this  leakage  is  afforded 
by  an  examination  of  the  blood  a  quarter  of  an  hour  after 
the  injection.  The  haemoglobin-  as  well  as  corpuscle-content 
is  found  to  have  largely  increased,  showing  that  the  greater 
part  of  the  fluid  of  the  defibrinated  blood,  which  was  intro- 
duced, has  already  escaped  out  of  the  vascular  system,  leaving 
behind  the  blood  corpuscles  and  a  certain  proportion  of  the 
proteins  of  the  plasma.  < 


THE  FLUID  BALANCE  OF  THE  BODY  137 

The  rise  of  capillary  pressure  occasions  also  a  more 
copious  glomerular  transudation,  and  therefore  an  increase 
in  the  excretion  of  urine.  The  extent  of  this  increase  differs 
according  to  the  composition  of  the  blood  which  has  been 
injected.  If  it  is  already  poor  in  water,  the  increased  urinary 
flow  may  be  minimal,  and  in  any  case  comes  to  an  end  or 
becomes  inappreciable  before  the  total  fluid,  which  has  been 
added  to  the  body,  has  been  eliminated.  This  is  not  sur- 
prising in  view  of  the  fact  that  the  leakage  of  fluid  from 
the  blood  vessels  causes  a  rise  in  the  concentration  of  the 
plasma  as  well  as  in  the  relative  proportion  of  red  blood 
corpuscles,  so  that  the  force  requisite  to  bring  about  filtration 
in  the  renal  glomeruli  must  be  increased  in  like  measure. 

The  concentration  of  the  blood,  resulting  from  the  leakage 
of  the  fluid  into  the  lymphatic  tissue  spaces,  raises  the  viscosity 
of  this  fluid,  and  therefore  the  resistance  to  its  flow  through 
the  capillaries.  If  the  injection  be  very  large,  this  resistance 
may  prove  too  much  for  the  heart ;  the  systolic  volume  of 
this  organ  becomes  larger  and  larger,  so  that  more  and  more 
blood  accumulates  behind  it  in  the  big  veins  and  liver,  and  its 
(distension  increases  between  each  beat;  finally  the  over-dilated 
heart  is  unable  to  effect  any  onward  movements  of  the  blood 
at  all,  and  the  animal  dies.  Bleeding  the  animal  under  these 
circumstances  brings  about  a  rapid  restoration  of  the  heart's 
functions  and  a  disappearance  of  all  dangerous  symptoms. 

If  we  use  normal  saline  fluid  instead  of  defibrinated  blood 
for  the  production  of  plethora,  we  obtain  a  condition  known  as 
hydraemic  plethora,  in  which  the  total  circulating  fluid  is 
increased,  but  the  relative  proportion  of  the  blood  corpuscles 
is  diminished,  and  the  protein-content  of  the  plasma  is  also 
below  normal.  Under  these  circumstances  the  organism  very 
rapidly  rids  itself  of  the  excess  of  fluid.  The  watery  plasma 
escapes  with  extreme  ease  into  the  tissue  spaces  and  into  the 


138 


THE    FLUIDS    OF    THE    BODY 


lymphatics.     The  blood  with  its  lower  viscosity  passes  readily 
through   the   dilated   arterioles  and   capillaries,  so  that  the 


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velocity  of  the  blood-flow  may  be  easily  increased  from  six  to 
ten  times.  The  kidney  swells  enormously,  and  the  rapid 
renewal  of  the  blood  in  its  vessels  provides  for  a  rapid  filtration 


THE  FLUID  BALANCE  OF  THE  BODY  139 

of  the  water  and  salts  of  the  dilute  plasma  through  the 
glomeruli.  Thus  in  most  cases  there  is  an  enormous  increase 
in  the  lymph  flow  from  the  thoracic  duct  as  well  as  in  the 
secretion  of  urine,  w^hich  in  each  case  lasts  just  so  long  as  the 
pressure  remains  above  normal  in  the  capillaries  concerned. 

The  course  of  the  pressure  in  different  parts  of  the  vascular 
system  after  a  large  injection  of  normal  salt  solution  is  shown 
in  the  accomj)anying  diagram  (Fig.  12).  Owing  to  the  greater 
ease  with  which  the  salt  solution  is  eliminated  from  the  circu- 
lating blood,  and  the  absence  therefore  of  concentration  of 
this  fluid,  w^e  may  inject  huge  quantities  into  the  circulation 
without  bringing  about  heart  failure.  Indeed,  if  the  injection 
be  carried  on  slowly,  the  kidneys  tend  to  secrete  at  the 
same  rate  as  the  salt  solution  is  allowed  to  flow  into  the 
jugular  vein. 

Anemia. 

By  anaemia  I  mean  a  diminution  in  the  total  volume  of  the 
circulating  blood,  involving  loss  both  of  plasma  and  of 
corpuscles,  such  as  may  be  brought  about  by  bleeding  the 
animal.  Some  of  the  effects  of  such  a  procedure  have  already 
been  studied  in  connection  with  the  phenomena  of  absorption 
by  the  blood  vessels.  As  regards  the  mechanical  conditions 
of  the  circulation,  loss  of  blood  by  haemorrhage  has  exactly  the 
reverse  influence  to  that  produced  by  plethora.  The  guiding 
principle  here,  as  there,  is  the  need  of  the  ruling  tissues 
of  the  body  for  a  constant  supply  of  oxygen,  and  therefore 
for  the  maintenance  of  a  normal  blood  supj^ly  through  the 
brain.  Owing  to  the  absence  of  vaso-motor  control  of  the 
intracranial  blood  vessels,  this  is  accomplished  through 
the  intermediation  of  the  arterial  pressure.  The  whole  aim 
of  all  the  mechanisms  set  in  action  by  change  in  the  volume 
of  the  circulating  fluid  is  the  maintenance  of  this  pressure. 
Loss   of  blood  is  therefore   followed   by   constriction  of  the 


140  THE  FLUIDS  OF  THE  BODY 

arterioles.  The  flow  through  all  the  capillaries,  except 
through  those  to  the  brain,  is  diminished,  the  pressure  in 
these  vessels  is  also  diminished,  and  there  is  a  fall  of  pressure 
in  the  great  veins  ojDening  into  the  auricles  as  well  as  in  the 
portal  vein.  The  arterial  side  of  the  circulation  is  kept  filled, 
so  far  as  possible,  at  the  expense  of  the  venous  side.  The  fall 
of  i)i'essure  in  the  capillaries  of  the  portal  system  and  in 
those  of  the  liver  causes  a  diminution  in  the  flow  of  lymph 
from  the  thoracic  duct.  In  the  same  way  the  urinary  flow 
may  be  diminished  or  abolished. 

More  important  is  the  rapid  emptying  of  the  tissue  spaces 
into  the  blood  vessels,  the  mechanism  of  which  we  have  already 
discussed.  As  a  consequence  of  this  passage  of  fluid  from 
tissue  spaces  directly  back  into  the  blood  vessels,  the  volume  of 
the  circulating  fluid  is  increased  towards  normal.  It  is  worthy 
of  note  that  this  passage  is  almost  immediate,  so  that  if  we 
bleed  an  animal,  say  to  300  cc,  the  last  50  cc.  of  blood  may 
be  appreciably  more  dilute  than  the  first  50  cc.  The  dilution 
of  the  blood  brought  about  in  this  way  is  however  limited. 
Comparative  estimates  of  the  composition  of  the  circulating 
fluid  from  determinations  made  five  minutes  after  bleeding 
and  twenty  minutes  after  bleeding  show  that  the  process 
is  practically  complete  at  the  first  period.  Moreover,  a  second 
and  third  bleeding  evoke  only  slight  further  changes  in  the 
concentration  of  the  blood. 

In  studying  the  alterations  in  the  composition  of  blood 
brought  about  by  bleeding,  it  is  necessary  to  take  precautions 
against  the  disturbing  influence  of  local  variations.  Where 
we  are  dealing  with  anaesthetised  animals,  the  fall  of  pressure 
consequent  on  the  anaesthetic  may  have  already  brought 
about  a  maximum  passage  of  fluid  from  tissue  spaces  into 
blood,  so  that  it  is  not  possible  to  evoke  any  further  dilution 
of  the  blood  as  the  result  of  bleeding.     In  animals  such  as  the 


THE    FLUID    BALANCE    OkF    THE    BODY  141 

horse,  where  sedimentation  of  corpuscles  occurs  easily,  the 
most  incongruous  results  may  be  obtained.  In  consequence 
of  the  passage  of  blood,  concentrated  by  sedimentation,  into 
the  general  circulation  after  the  bleeding,  we  may  indeed 
obtain  an  apparent  concentration  of  the  whole  blood  instead 
of  the  expected  dilution. 

In  the  normal  animal  the  process  of  absorj)tion  of  the  tissue 
fluids  creates  in  all  the  tissues  a  need  for  more  fluid,  which, 
in  the  presence  of  the  higher  nervous  system,  is  interpreted 
as  thirst.  The  intake  of  the  fluid  by  the  intestines  is  therefore 
increased.  Thus  the  process  of  dilution  of  the  blood  proceeds, 
first  at  the  expense  of  the  tissue  fluid  and  then  at  the  expense 
of  the  fluid  absorbed  from  the  gut,  until  the  dilution  of  the 
plasma  is  sufficiently  advanced  to  make  up  the  total  volume' 
of  circulating  blood  to  normal.  When  this  has  occurred,  the 
secretions  of  lymph  and  of  urine  resume  their  normal  course, 
and  indeed  are  rather  more  pronounced  than  before  on  account 
of  the  greater  ease  of  transudation  of  the  more  watery  plasma. 

A  considerable  time,  days  or  weeks,  may  elapse  before  the 
blood  attains  the  same  constitution  as  it  had  before  the 
bleeding.  Of  the  seat  and  mode  of  formation  of  the  plasma- 
constituents  we  know  nothing.  The  loss  in  red  corpuscles  is 
made  uj)  by  increased  activity  of  the  blood-forming  tissue  in 
the  bone  marrow,  and  there  seems  every  reason  to  believe  that 
the  stimulus  to  this  increased  activity  of  the  marrow  is  to  be 
found  in  the  reduced  oxygen  tension  of  the  blood  passing 
through  this  tissue.  Each  unit  volume  of  the  blood  carries 
less  oxygen  than  would  be  carried  by  a  blood  containing  the 
normal  percentage  of  haemoglobin,  so  that  the  amount  of  this 
gas  and  its  tension  must  be  diminished  more  rapidly  as  the 
blood  flows  through  the  tissue  than  would  be  the  case  under 
normal  circumstances.  The  influence  of  lack  of  oxygen  in 
exciting  activity  of  the  bone  marrow  has  been  demonstrated 


142  THE  FLUIDS  OF  THE  BODY 

in  various  ways.  In  the  first  place  we  have  the  real  hyper- 
troj)hy  of  the  blood  which  occurs  as  the  result  of  continued 
residence  in  high  altitudes,  i.e.,  at  low  oxygen  tensions.  A 
similar  effect  to  bleeding  can  be  brought  about  by  cutting  out 
of  function  a  certain  j)i'oportion  of  the  red  corpuscles,  as, 
e.g.,  by  partial  poisoning  with  CO  gas.  It  has  been  shown  by 
Nasmith  and  Graham*  that  a  condition  of  plethora,  or  at  any 
rate  an  increased  formation  of  red  corpuscles  and  of  hsemo- 
globin,  may  be  induced  in  animals  by  chronic  poisoning  with 
this  gas. 

It  is  important  therefore  to  remember  that  any  factor,  which 
tends  to  diminish  the  oxygen  tension  of  the  circulating  blood, 
will  tend  to  produce  at  the  same  time  increased  formation  of 
red  corpuscles  and  of  hemoglobin.  As  a  result  of  bleeding 
however,  we  get  not  merely  increased  production  of  corpuscles. 
In  all  probability  the  stimulus  is  also  effective  on  those 
tissues  of  the  body  which  are  engaged  in  building  up  the 
proteins  of  the  plasma,  so  that  one  may  speak  of  bleeding  as 
affording  a  stimulus  to  the  whole  of  the  assimilative  functions 
of  the  body,  which  is  analogous  in  almost  all  respects  to 
that  experienced  as  the  result  of  residence  in  high  altitudes. 
Zuntzf  and  his  school  have  shown  that  the  effects  of  mountain 
air  are  apparent,  not  only  in  their  influence  on  red  corpuscles, 
but  also  on  the  nitrogenous  metabolism  of  the  body  as  a 
whole,  so  that  there  is  in  most  individuals  a  positive  nitrogen 
balance,  an  actual  reproduction  of  the  conditions  found  in  the 
growing  organism.  We  are  thus  literally  correct  when  we 
speak  of  the  rejuvenating  effects  of  a  holiday  spent  in  the 
mountains.  Before  the  application  of  steam  and  other  agencies 
to  the  facilitation  of  methods  of  transit,  which  has  occurred 

*  Journ.  of  Physiol.,  XXXY.,  32,  1906. 

t  See  especially  "  Hohenklima  und  Bergwanderungen,"  by  Zuntz, 
Loewy,  Miiller,  and  Caspari.     Berlin,  1906. 


THE  FLUID  BALANCE  OF  THE  BODY  143 

during  the  last  century,  this  rejuvenating  effect  was  obtained  by 
the  practice  of  bleeding,  the  beneficial  results  of  which  had  been 
discovered  empirically.  The  blood-letting  in  the  spring  and 
at  the  fall  called  into  play  those  recuperative  processes  of  the 
organism  w4iich  we  now  seek  to  stimulate  by  a  trip  to 
Switzerland  or  to  the  Kockies.  It  is  probable  that,  with  the 
recognition  of  the  physiological  effects  of  loss  of  blood,  the 
practice  of  occasional  blood-letting  may  be  restored  to  the 
position  of  honour  which  it  held  in  medical  practice  before 
it  had  been  discredited  by  its  employment  as  a  panacea  for  all 
forms  of  disorder. 

The  mechanisms,  which  determine  the  adaptation  of  the 
organism  to  changes  in  the  total  volume  of  its  fluid  content, 
must  come  into  play  with  every  rise  or  fall  in  general  blood 
pressure.  Thus  any  marked  alteration  in  the  local  distribution 
of  the  blood  must  bring  about  changes,  not  in  the  total 
volume  of  the  body  fluid,  but  in  the  distribution  of  this  fluid 
between  the  blood  and  the  tissues.  The  blood  pressure  of 
man  is  continually  varying.  The  normal  systolic  pressure  in 
the  brachial  artery,  when  the  man  is  at  rest,  is  about  110  mm. 
Hg.  The  slightest  excitement  or  concentration  of  attention 
may  increase  this  pressure  by  20  or  30  mm.,  and  in  active 
exercise  there  may  be  a  rise  of  blood  pressure  to  between  150 
and  200  mm.  Hg.  due,  partly  to  the  mechanical  influence  of 
the  muscular  and  respiratory  movements  on  the  circulation, 
partly  to  mechanical  stimulation  of  the  medullary  centres 
by  metabolites  produced  in  the  contracting  muscles. 

How  will  such  a  rise  affect  the  distribution  of  fluid  ?  It  has 
been  pointed  out  that  violent  exercise,  such  as  sprinting  one 
hundred  yards,  will  raise  the  corpuscle  content  of  the  blood 
10  or  15  per  cent.  According  to  Oliver,  every  rise  of  pressure 
brought  about  by  exercise  of  short  duration  causes  a  con- 
centration of  the  blood  and  an  increase  of  the  fluid  in  the 


144  THE  FLUIDS  OF  THE  BODY 

tissue  spaces  of  the  finger.  A  similar  temporary  rise  of 
pressure  may  be  produced  in  an  animal  by  injection  of 
adrenalin.  According  to  Hess,*  such  a  rise  causes  a  con- 
centration of  the  blood  in  the  veins  of  the  body,  but  no 
change  in  the  blood  of  the  arterial  system.  This  author 
therefore  concludes  that  the  lost  fluid  is  made  up  to  the  blood 
in  its  passage  through  the  lungs.  I  have  been  unable  to 
obtain  evidence  of  any  such  regulating  function  of  the  lungs. 
In  every  case  a  rise  of  pressure  evoked  by  the  injection  of  a 
small  dose  of  adrenalin  causes  a  concentration  of  the  blood  in 
the  arteries  as  well  as  in  the'^^eins. 

On  the  other  hand,  a  fall  of  pressure,  however  produced, 
whether  by  chloroform  narcosis,  by  heart  failure,  or  by  section 
of  the  spinal  cord,  causes  a  dilution  of  the  blood  by  the  same 
mechanism  as  that  involved  in  the  making  up  of  the  volume 
of  the  circulating  fluid  which  occurs  after  bleeding.  The 
same  condition  may  be  brought  about  by  altering  the  dis- 
tribution of  blood  within  the  body.  Thus  obstruction  of  the 
inferior  vena  cava  above  the  liver  causes  increased  concentra- 
tion of  the  blood  below  the  obstruction  and  a  large  increase  in 
the  lymph  production  within  the  liver.  The  plasma  of  the 
blood  circulating  through  the  rest  of  the  body,  i.e.,  in  a  sample 
taken  from  the  carotid  or  femoral  artery,  is  found  to  be  more 
dilute  than  at  the  beginning  of  the  experiment.  Lowering  of 
pressure  therefore  causes  passage  of  fluid  from  the  tissue 
spaces  into  the  capillaries  ;  raising  the  arterial  pressure  causes 
increase  of  tissue  fluid  at  the  expense  of  the  plasma. 

Almost  every  observer  has  described  a  sudden  increase  in 
the  relative  number  of  corpuscles  of  the  blood  as  the  result  of 
removal  to  high  altitudes,  or  diminution  of  the  tension  of  the 
oxygen  in  the  blood.     There  seems  to  be  little  doubt  that  this 

-  Schmiedeberg's  Archiv,  LXXIX.,  128,  1903. 


THE  FLUID  BALANCE  OF  THE  BODY  145 

immediate  increase  of  corpuscles,  which  is  too  sudden  to  be 
accounted  for  by  increased  activity  of  the  blood-forming 
tissues,  must  be  ascribed  to  a  diminution  of  the  plasma  of  the 
blood,  accompanied  perhaps  by  a  corresponding  increase  of 
the  fluid  in  the  connective  tissue  spaces.  The  cause  of  this 
change  in  the  blood  is  not  yet  understood.  It  might  be 
accounted  for  if  the  increased  arterial  pressure  recorded  by 
some  observers  as  the  result  of  removal  to  high  altitudes  were 
a  constant  phenomenon,  but  I  myself  have  been  unable  to 
find  any  appreciable  change  in  the  normal  pressure  on  removal 
from  the  plains  to  the  mountains. 

On  the  other  hand,  the  processes,  which  we  have  been  con- 
sidering, play  an  important  part  in  determining  the  course  of 
events  in  cases  of  heart  disease  (especially  in  cases  where  there 
is  failure  of  compensation),  and  are  responsible  for  many  of 
the  consequences  or  concomitants  of  such  a  disorder.     The 
use  of  the  heart-pump  is  to  maintain  a  constant  passage  of 
blood  from  the  venous  to  the  arterial  side  of  the  vascular 
system ;  taking  it  from  the  former  at  a  low  pressure,  it  pumps 
it  into  the  arterial  system  at  a  high  pressure.     Any  failure  of 
the  pump  ought  therefore  to  tend  to  equalisation  of  pressure 
on  the  two  sides  of  the  system,  i.e.,  to  a  fall  of  arterial  and  a 
rise  of  venous  pressure.     Such  a  change  in  the  pressures  can 
be  shown  to  be  produced  when  the  heart's  action  is  interfered 
with  by  stimulation  of  the  vagus,  or  by  the  injection  of  fluid, 
such  as  oil,  into  the  pericardium  so  as  to  diminish  the  diastolic 
expansion  of  the  heart.     Since  engorgement  of  the  veins  and 
a  weak  fluttering  pulse  are  frequently  observed  in  heart  disease 
when  there  is    failure  of  compensation,  it  was  assumed  by 
Cohnheim,*  and  more  or  less  accepted  by  most  clinical  patho- 
logists for  many  years,  that  the  condition  in  such  disorders 


-  Cohnheim's  "  Lectures  on  General  Pathology  "  (New  Syd.  Soc,  1889). 
F.B.  L 


146  THE  FLUIDS  OF  THE  BODY 

is  exactly  comparable  to  that  which  may  be  produced 
in  the  laboratory  by  the  injection  of  oil  into  the  pericardium. 
In  this  case,  as  soon  as  sufficient  oil  has  been  introduced 
to  interfere  with  the  normal  diastolic  expansion  of  the 
heart,  the  pressure  is  seen  to  fall  in  the  arteries,  and  to 
rise  in  the  veins.  At  a  certain  point  where  interference  with 
the  heart's  action  becomes  dangerous  for  life,  even  in  the 
morphinised  animal,  there  is  a  very  sudden  rise  of  venous 
pressure,  especially  marked  in  the  portal  vein,  brought  about 
by  the  ansemic  stimulation  of  the  vasomotor  centres  and  the 
universal  vascular  constriction  thereby  produced. 

Only  within  recent  years  has  the  applicability  of  the  analogy 
with  experimental  conditions  been  put  to  a  test  by  actual 
measurement  of  the  arterial  pressure  in  cases  of  heart  disease. 
A  series  of  observations  of  this  description  was  made  by  Dr. 
H.  J.  Starling*  on  cases  in  the  Norwich  Hospital.  The  sur- 
prising fact  was  elicited  that  in  no  case  of  heart  disease, 
however  severe  the  symptoms  and  however  marked  the 
failure  of  compensation,  was  the  blood  pressure  in  the  arteries 
below  the  normal.  Only  just  before  death  occurred  was  a 
gradual  fall  of  pressure  to  be  observed.  In  fact,  as  he 
has  shown,  we  may  divide  cases  of  heart  disease  into  two 
classes  :  those  in  which  the  arterial  pressure  is  normal ;  and 
those,  chiefly  occurring  in  older  subjects,  in  which  the  pressure 
is  very  high  and  may  amount  to  over  200  mm.  Hg.  In  the 
latter  class,  it  is  probable  that  we  must  ascribe  to  the  rise  of 
pressure  itself  the  production  of  lesions  in  the  heart  muscle 
and  the  ultimate  failure  of  its  action. 

But  the  question  arises  :  why  does  not  failure  of  the  heart- 
pump  bring  about  a  fall  of  arterial  pressure  ?  Why  is  it  that 
in  cases  of  heart  disease  we  find  a  normal  arterial  pressure, 


*  H.  J.  Starling,  Lancet,  Sept.  29,  1906, 


THE  FLUID  BALANCE  OF  THE  BODY  147 

even  when  there  is  considerable  over-distension  of  the  veins  ? 
The  responsible  factor  in  determining  the  state  of  things  has 
already  been  mentioned.  The  whole  vascular  system  is 
subordinate  in  its  activity  to  the  needs  of  the  master  tissue  of 
the  body,  viz.,  the  brain.  For  these  needs  a  certain  height 
of  arterial  pressure  is  essential  in  order  that  the  medullary 
centres  shall  receive  a  proper  supply  of  blood  and  of  oxygen. 
Whatever  the  working  capacity  of  the  heart,  the  brain  will 
insist  on  having  its  proper  supply  of  blood,  failure  of  this  for 
a  short  time  being  followed  by  the  death  of  the  animal. 

What  then  is  the  result  of  temporary  failure  of  the  heart- 
pump  ?  We  have  some  clue  to  this  in  the  experiment  already 
described  on  the  injection  of  oil  into  the  pericardium.  As 
soon  as  the  arterial  pressure  falls  so  low  as  to  cause  an 
ischaemia  appreciable  by  the  vasomotor  centre,  the  latter  at 
once  sends  down  by  all  the  vascular  nerves  impulses  which 
bring  about  universal  vaso-constriction.  If  this  is  not 
sufficient  to  raise  the  arterial  pressure,  increased  respirations 
and  expiratory  convulsions  occur,  and  tend  to  force  the  blood 
from  the  veins  into  the  heart,  thereby  increasing  the  output  of 
the  latter.  Of  course,  in  the  experiment  under  consideration, 
an  increased  output  is  impossible,  since  we  have  artificially 
prevented  the  heart  from  receiving  during  diastole  more 
than  a  certain  small  quantity  of  blood.  The  effort  however 
to  get  the  blood  from  the  venous  into  the  arterial  side  is 
present,  and  will  be  effective  if  the  heart  failure  is  brought 
about,  not  by  distension  of  the  pericardium,  but  by  diminished 
emptying  of  the  heart  in  systole. 

Let  us  consider  first  the  reaction  of  the  heart  to  a  sudden 
increase  in  the  demands  made  upon  it.  If  both  splanchnic 
nerves  be  stimulated  with  a  strong  current,  a  large  increase  in 
the  resistance  to  the  outflow  of  the  blood  is  at  once  produced. 
By  enclosing  the  heart  in  a  plethysmograph  we  may  record 

L  2 


148  THE  FLUIDS  OF  THE  BODY 

its  behaviour  under  these  conditions.  The  first  effect  is  that 
the  emptying  of  the  heart  is  less  effective.  Its  systolic  volume 
is  increased.  The  rise  of  pressure  however  determines  also 
a  rise  of  pressure  on  the  venous  side,  and  during  diastole  the 
heart  receives  more  blood,  in  addition  to  the  quantity  of  blood 
which  it  contains  at  the  beginning  of  diastole,  as  the  result  of 
partial  failure  in  previous  systole.  Its  diastolic  volume  is 
therefore  also  increased. 

For  the  next  two  or  three  beats  the  heart  dilates  with  each 
beat,  being  unable  to  expel  its  contents  against  the  high 
arterial  pressure,  and  the  dilatation  is  favoured  by  the  fact  that 
at  the  beginning  of  each  systole  the  heart  contains  more  blood 
than  under  normal  circumstances.  The  increase  in  diastolic 
distension  acts  however  as  a  direct  stimulus  to  the  heart 
muscle,  increasing  its  capacity  for  work,  while  the  high  arterial 
pressure  quickens  the  flow  through  the  coronary  arteries  and 
therefore  in  this  way  also  improves  the  capacity  of  the  heart 
muscle.  As  the  result  of  the  improved  nutrition  and  the 
increased  excitation,  the  output  of  the  heart  at  each  beat  con- 
tinually increases,  and  after  about  half  a  dozen  to  a  dozen  beats 
we  find  that  the  expulsive  effort  of  the  heart  is  so  successful 
that  it  attains  its  previous  systolic  volume,  although  it  is  putting 
out  an  increased  amount  of  blood  at  each  beat  (Fig.  13). 

The  heart  therefore  finally  reinforces  the  constriction  of  the 
arterioles  in  maintaining  the  high  arterial  blood  pressure. 
If  the  vagi  are  intact,  this  recovery  of  the  cardiac  systolic 
volume  may  be  hindered,  the  heart  itself  automatically  and 
reflexly  trying  to  spare  its  activities.  If  a  valve  be  damaged 
in  a  normal  heart,  we  generally  find  that  the  compensation, 
determined  by  the  increased  diastolic  filling  of  the  affected 
cavity,  is  so  complete  that  practically  no  change  occurs  in  the 
arterial  pressure.  The  heart  does  more  work,  and  in  time 
its   muscle-fibres   become  hypertrophied.      If   this  increased 


THE  FLUID  BALANCE  OF  THE  BODY 


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work  be  interfered  with  by  simultaneous  change  in  the 
heart  muscle,  as  may  occur  in  rheumatic  myocarditis,  we 
may   imagine   failure   of    compensation  occurring    for    some 


150 


THE    FLUIDS    OF    THE    BODY 


little  time.  How  will  the  organism  react  to  such  failm^e  ? 
Every  failure  of  the  heart-pump  tends  to  bring  about  a  lower 
arterial  and  a  higher  venous  pressure.  The  heart  wall 
therefore  becomes  more  and  more  distended  during  diastole 
until  the  extra  stimulus  applied  by  the  distension  is  sufficient 
to  equalise  the  output  of  the  heart  to  its  intake  during 
diastole.  The  maintenance  of  an  adequate  output  involves 
therefore  a  continuance  of  the  high  venous  pressure,  which  can 
only  be  secured  simultaneously  with  the  maintenance  of  a 
normal  arterial  pressure  by  the  universal  vascular  constriction. 
The  condition  indeed  is  analogous,  in  the  arteries  and 
capillaries,  to  that  produced  by  bleeding,  although  in  the  case 
of  heart  failure  the  vascular  system  is  bled  into  the  veins  and 
cardiac  cavities  instead  of  the  blood  being  lost  to  the  body  as 
a  whole.  Now  every  lowering  of  arterial  pressure,  and 
especially  of  capillary  pressure,  causes  increased  absorption 
from  the  tissues.  The  constriction  of  the  vessels  of  the 
splanchnic  area  may  be  expected  (though  this  is  not  yet 
proved),  to  enhance  the  rate  of  absorption  of  water  from  the 
alimentary  canal,  while  the  lowered  pressure  in  the  renal 
capillaries  and  the  diminished  rate  of  flow  will  lessen 
the  output  of  fluid  from  the  body.  Finally  therefore  the 
necessary  increased  diastolic  filling  of  the  heart  brought  about 
by  a  rise  of  venous  pressure,  but  associated  with  the  normal 
arterial  pressure  demanded  by  the  brain,  can  be  maintained 
only  by  increasing  the  intake  as  compared  with  the  outj)ut 
of  fluid  by  the  body  as  a  whole.  The  total  volume  of  circu- 
lating fluid  must  be  increased. 

We  might  therefore  expect  to  find  that  a  condition  of 
hydraemic  plethora  would  be  set  up.  Clinical  investigation 
in  cases  of  heart  disease  or  failure  of  compensation  does  not 
however  reveal  increased  dilution  of  the  blood,  such  as 
we  might  expect  if  the  foregoing  argument  were  correct  or 


THE  FLUID  BALANCE  OF  THE  BODY  151 

complete.  Although  in  some  cases  a  relative  paucity  of 
red  corpuscles  may  be  found,  in  many  others  the  haemo- 
globin content  of  the  blood  is  normal,  or  even  somewhat 
increased.  This  might  have  been  prophesied  if  we  had  taken 
into  account  another  factor,  w^hich  is  the  determining  con- 
dition for  the  production  of  red  corpuscles.  The  activity  of 
the  red  bone  marrow  can  be  excited  by  any  change  in  the 
animal  which  lowers  the  tension  of  the  oxygen  in  the  blood 
coming  to  this  tissue,  whether  it  be  diminution  of  the  total 
amount  of  haemoglobin,  such  as  that  produced  by  bleeding, 
or  exposure  of  the  animal  to  atmospheres  with  deficient  oxygen 
tension.  In  cases  of  partial  heart  failure,  the  arterial  pres- 
sure is  kept  up  only  at  the  expense  of  the  escape  of  blood 
from  the  arterial  to  the  venous  side,  a  slowing  w^hich  is 
felt  all  round  the  system  and  affects  the  total  circulation 
time.  Moreover  in  many  cases  there  is  actual  interference 
with  the  functions  of  the  lung  in  consequence  of  the  en- 
gorgement of  its  vessels.  Cyanosis,  i.e.,  deficient  aeration 
of  the  blood,  is  therefore  a  constant  symptom  of  deficient 
cardiac  action.  Chronic  cyanosis  must  have  the  same  effect 
as  chronic  poisoning  with  CO  gas,  or  exposure  to  an  atmosphere 
of  low  oxygen  tension,  viz.,  a  direct  excitation  of  the  function 
of  the  bone  marrow  and  increased  production  of  red  corpuscles. 
We  have  thus,  in  failure  of  compensation,  a  combination  of 
factors,  one  set  of  which  determines  an  increase  in  the  fluid 
constituents  of  the  blood,  the  other  set  an  increase  in  the  red 
blood  corpuscles.  As  the  result  a  condition  of  real  plethora 
is  set  up ;  and  the  vascular  system  contains  an  excess  of 
blood  of  normal  concentration  and  composition. 

In  the  case  of  anaemia  by  haemorrhage  we  found  that  the 
diminution  in  the  tissue  fluid,  which  was  the  immediate 
effect  of  the  bleeding,  was  rapidly  made  good  in  a  healthy 
animal  by  increased  intake    of   fluid  as  compared  with  the 


152  THE  FLUIDS  OF  THE  BODY 

output.  On  the  day  after  the  bleeding  the  animal  would 
already  possess  a  normal  blood  pressure,  as  well  as  a  normal 
state  of  distension  of  its  tissue  spaces.  The  same  thing  must 
occur  in  the  case  of  failure  of  compensation.  The  disturbed 
balance  between  intra-  and  extra-  vascular  fluid  is  rapidly 
made  good,  so  that  finally  the  sole  factors  which  we  have  to 
take  into  account  are  those  of  intake  and  output  of  fluid. 
The  amount  of  fluid  in  the  body  will  continue  to  increase 
so  long  as  the  heart  is  inefficient,  and  the  condition  of 
plethora  will  persist  even  when  the  balance  between  the 
intra-  and  extra-  vascular  fluid  begins  to  be  upset  in  the 
opposite  direction,  viz.,  in  the  production  of  increased  transu- 
dation. Thus  in  many  cases  the  patient  finally  becomes 
waterlogged.  Not  only  is  the  volume  of  the  circulating  fluid 
increased,  but  all  his  tissues  are  filled  to  distension  with 
dropsical  fluid,  in  the  production  of  which  the  increased 
filling  of  the  vascular  system  as  a  whole  must  play  an 
important  part. 

It  is  now  many  years  since  I  pointed  out  that  the  physio- 
logical factors  at  work  in  failure  of  compensation  must  finally 
determine  a  true  plethora,  and  the  existence  of  this  plethora  has 
been  in  late  years  directly  demonstrated  by  Lorrain  Smith* 
with  the  aid  of  Haldane's  carbon-monoxide  method.  Moreover 
it  is  only  by  the  existence  of  an  increased  filling  of  the  vascular 
system  that  we  can  account  for  the  co-existence  of  a  normal 
arterial  pressure  with  distension  of  the  veins  throughout  the 
whole  body,  and  a  rise  of  pressure  within  these  vessels.  In 
my  next  lecture  we  shall  have  to  consider  in  greater  detail 
the  manner  in  which  the  distension  of  the  tissue  spaces  with 
fluid,  i.e.,  the  dropsy  of  heart  disease,  is  brought  about. 

Among  the  factors  determining  the  production  and  absorption 


-  Trans.  Path.  Soc.  LIII.,  p.  136,  1902. 


THE  FLUID  BALANCE  OF  THE  BODY  153 

of  tissue  fluid,  considerable  importance  must  be  attached  to 
chemical  changes  in  the  tissues  or  in  the  blood,  and  such 
chemical  changes  must  also  be  assumed  to  play  a  part  in  the 
determination  of  alterations  in  the  total  fluid  content  of  the 
body  both  m  health  and  in  disease.  Our  knowledge  of  these 
factors  is,  however,  much  more  scanty  than  is  the  case  with 
the  mechanical  conditions  which  we  have  just  been  considering. 
The  general  character  of  their  influence  will  be  evident  from  a 
study  of  certain  conditions  which  may  be  experimentally  pro- 
duced. Let  us  take,  for  example,  the  effects  of  increasing  the 
crystalloid  content  of  the  blood  by  the  injection  of  a  concen- 
trated solution  into  the  blood  stream.  If  a  solution  of  30  grs. 
of  glucose  in  about  30  cc.  of  water  be  injected  into  the 
jugular  vein,  the  first  effect  is  a  great  increase  in  the  volume 
of  the  circulating  blood,  brought  about  by  the  osmotic  attrac- 
tion of  w^ater  into  the  vessels  at  the  expense  first  of  the  tissue 
spaces,  but  ultimately  of  the  tissue  cells.  The  consequence 
of  the  hydraemic  plethora  thereby  induced  is  increased  circu- 
lation through  the  kidneys  and  increased  output  of  urine 
containing  large  quantities  of  sugar.  The  sugar  has  a  direct 
influence  on  the  kidney  vessels,  or  possibly  on  the  kidney 
cells,  so  that  the  diuresis  endures  long  after  the  total  volume 
of  the  circulating  blood  has  been  restored  to  normal.  Finally, 
when  the  flow  of  urine  slows  down,  the  blood  has  been 
concentrated  to  a  point  considerably  above  normal.  Under 
ordinary  circumstances  the  concentration  of  the  tissues  thus 
induced  w^ould  produce  intense  thirst  and  increased  intake 
of  water,  so  that  the  urinary  flow  would  be  maintained  at  a 
high  level  until  the  whole  excess  of  the  glucose  had  been 
excreted. 

Similar  effects  would  be  induced  with  injection  of  sodium 
sulphate.  When  sodium  chloride  however  is  injected  into 
the  blood  vessels,  it  escapes  with  such  ease  into  the  tissues 


154  THE  FLUIDS  OF  THE  BODY 

that  the  total  hydrsemic  plethora  produced  is  less  than  with 
injection  of  glucose  or  sodium  sulphate.  Moreover  this  salt 
appears  to  exercise  little  or  no  specific  influence  on  the  kidney 
vessels  or  cells,  so  that  the  diuresis  comes  to  an  end  as  soon 
as  the  hasmoglobin  content  of  the  blood,  and  therefore  its 
volume,  has  been  restored  to  normal.  On  the  other  hand, 
the  greater  molecular  concentration  of  the  tissues,  caused 
by  the  escape  into  them  of  the  salt,  will  produce  thirst 
and  increased  intake  of  fluid  until  their  concentration  is 
reduced  to  normal.  The  absence  of  the  diuretic  effect 
implies  that  there  is  no  driving  force  pumping  the  excess 
of  sodium  chloride  out  of  the  blood,  and  therefore  out  of 
the  tissues.  These  indeed  seem  to  possess  but  little  sensitive- 
ness towards  the  presence  of  the  salt,  which  forms  the  most 
abundant  constituent  of  their  normal  medium. 

It  is  a  familiar  circumstance  that  the  ingestion  of  an 
excessive  quantity  of  salt  provokes  thirst  rather  than  diuresis. 
If  this  excessive  ingestion  were  continued  or  became  chronic, 
there  would  be  a  tendency  for  the  amount  of  this  salt  in  the 
body  to  continually  increase,  the  salt  being  associated  with 
sufficient  water  to  maintain  the  molecular  concentration  of 
the  body  fluids  at  their  normal  height.  It  is  not  surprising 
therefore  that  excessive  quantities  of  salt  have  been  found  to 
exert  a  deleterious  influence  in  cases  of  dropsy,  or  that 
marked  benefits  as  regards  the  reduction  of  dropsy  have  been 
attained  by  the  limitation  of  salt  in  the  diet. 

Similar  chemical  factors  might  be  involved  in  other  cases, 
either  where  there  is  increase  of  the  total  fluid  of  the  body 
without  evident  oedema,  as  in  chlorosis,  or  in  the  universal 
oedema  which  occurs  in  Bright's  disease.  The  responsible 
factor  in  these  cases  might  be  either — 

(a)  The  production  of  some  substance  of  low  molecular 
weight  which  could  be  easily  distributed  through  the  tissues 


THE  FLUID  BALANCE  OF  THE  BOD'S  155 

and  add  to  their  molecular  concentration,  but  which  had 
no  specific  diuretic  effect,  or — 

(b)  A  retention  of  the  normal  constituents  of  the  body  in 
consequence  of  deficient  excretion  by  the  kidneys. 

The  causation  of  the  dropsy  in  Bright' s  disease  is  at 
present  enshrouded  in  ignorance,  and  we  cannot  yet  say 
how  far  it  is  really  comparable  to  the  waterlogged  condition 
of  the  body  which  may  be  brought  about  by  over-feeding 
with  sodium  chloride.  It  is  important  to  remember  that  in 
every  case,  where  we  have  disturbance  of  the  balance  between 
intra-  and  extra-  vascular  fluid,  or  of  the  balance  between  the 
intake  and  output  of  fluid  into  or  from  the  body  as  a  whole, 
we  must  take  into  account  not  only  the  mechanical  conditions 
which  determine  transudation  and  absorption,  but  also  the 
possible  effects  of  chemical  substances  in  their  relation  to 
excretion  and  absorption,  as  well  as  to  the  vitality  of  the 
capillary  walls  and  tissue  cells.  Only  by  keeping  these 
possible  factors  in  view  can  we  hope  to  arrive  at  some  solu- 
tion of  the  difficulties  which  present  themselves  when  we 
attempt  to  account  for  the  occurrence  of  dropsy  in  its 
manifold  forms. 


LECTUEE   YlII 


THE    CAUSATION    OF    DROPSY 


From  the  practical  point  of  view,  the  most  interesting  and 
important  pathological  alteration  in  the  distribution  of  the 
fluids  of  the  body  is  to  be  found  in  the  condition  known  as 
dro23sy.  The  term  dropsy  may  be  used  to  denote  either  an 
increased  amount  of  fluid  in  the  connective  tissue  spaces,  espe- 
cially of  the  skin,  when  it  is  sometimes  designated  as  anasarca 
or  oedema,  or  an  accumulation  of  fluid  in  the  serous  spaces 
of  the  body,  as  in  the  conditions  of  hydrothorax  and  ascites. 
In  some  cases  the  production  of  oedema  may  be  brought 
about  by  local  changes,  and  therefore  involve  merely  a 
different  distribution  of  the  body  fluid.  Often  however,  the 
increase  of  fluid  in  the  connective  tissue  spaces,  including  the 
serous  spaces,  is  more  or  less  general,  and  may  be  associated 
with  a  simultaneous  increase  of  the  other  chief  fluid  of  the 
body,  namely,  the  blood.  Our  previous  studies  enable  us  to 
enumerate  a  number  of  factors  which  might  possibly  be  in- 
volved in  the  flooding  of  the  tissue  spaces  which  is  charac- 
teristic of  dropsy.  I  have  drawn  up  a  list  of  these  factors 
in  the  form  of  a  Table,  and  it  will  be  my  office  in  this  lecture 
to  attempt  to  assign  to  each  of  them  its  relative  importance. 

Factors  involved  in  the  Causation  of  Dropsy. 

I.  Factors  causing  increased  transudation:— 

A.  Increased  intra-capillary  pressure  : 
a.  Venous  obstruction. 
I.  Vasodilatation, 
c.  Plethora. 


THE    CAUSATION    OF    DROPSY  157 

I.  Factors  causing  increased  trB^nsMdsition— continued. 

B.  Increased  permeability  of  vessel  wall : 

a.  Local  injury  by  mechanical  irritants. 

,,    thermal  „ 

,,  ,,        ,,   chemical  ,, 

b.  Malnutrition. 

c.  General  injury  by  circulating  poisons  (?). 

C.  Watery  condition  of  blood  (hydraemia). 

D.  Increased  molecular  concentration  of  tissues. 

II.  Factors  causing  diminished  absorption:— 

A.  By  lymphatics : 

a.  Paralysis  of  limbs. 

&.  Obstruction  of  lymphatic  trunks. 

B.  By  veins : 

a.  Venous  obstruction . 

h.  Watery  condition  of  blood. 

c.  Concentrated  transudations  {i.e.  in  protein). 

It  is  important  to  remember  that  probably  under  no  cir- 
cumstances can  dropsy  be  ascribed  to  an  abnormal  change  in 
one  only  of  these  processes.  This  however  can  also  be  said 
of  any  other  diseased  condition  of  the  body.  We  know  that 
the  organism  responds  to  a  destruction  of  a  considerable  part 
of  the  excretory  apparatus  of  the  kidney  by  sending  up  the 
general  blood  pressure,  and  so  driving  an  increased  amount 
of  blood  through  the  still  healthy  glomeruli.  But  we  cannot 
say  that  two-thirds  of  the  kidneys  are  practically  inactive 
under  normal  conditions,  because  excision  of  two-thirds 
causes  no  change  in  the  general  condition  of  the  animal  nor 
any  appreciable  heaping  up  of  urea  in  the  blood.  In  the 
same  way  we  find  that  the  organism  has  various  powers  of 
accommodating  itself  to  changed  conditions  in  its  lymphatic 
apparatus,  so  that  it  is  in  most  situations  difficult  to 
upset  the  normal  balance — i.e.,  cause  dropsy — by  altering 
only  one  of  these  factors,  unless  the  alteration  be  of  a 
very   extreme   degree.     In   nearly    all  cases    the    dropsy   is 


158  THE  FLUIDS  OF  THE  BODY 

due  to  the  simultaneous  alteration  of  two  or  more  of  these 
factors.  In  the  following  lecture  I  shall  try  to  show,  so  far 
as  our  imperfect  experimental  knowledge  allows,  which  of 
these  factors  are  affected  in  the  chief  forms  of  dropsy  known 
clinically,  and  also  to  show  how  the  normal  balance  between 
production  and  absorption  has  been  in  each  case  upset. 

The  form  of  dropsy  which  is  simplest  in  its  pathology  is 
that  which  is  due  to  venous  obstruction.  Clinically  one  meets 
with  dropsy  of  one  extremity  due  to  obstruction  of  the  veins 
draining  that  part,  either  in  consequence  of  pressure  by 
growths,  or  of  thrombosis  occurring  in  the  vein  itself.  It 
would  be  natural  to  ascribe  this  dropsy  to  the  increased 
lymph  production  consequent  on  the  raised  intra-capillary 
pressure  behind  the  obstruction.  On  investigating  the  subject 
experimentally  however,  one  finds  that  the  causation  is 
not  quite  so  simple.  Here,  as  in  nearly  all  other  cases,  more 
than  one  factor  is  at  work.  It  is  a  well-known  fact  that 
although  obstruction  of  the  femoral  vein  by  a  thrombus  may 
give  rise  to  pronounced  oedema  of  the  leg,  yet  ligature  of  the 
femoral  vein  or  even  of  the  lower  end  of  the  inferior  vena 
cava  in  dogs  produces  no  oedema  of  the  legs.  Thus  Lazarus 
Barlow*  found  that  elastic  constriction  of  the  veins  of  a  limb, 
sufficient  to  cause  a  considerable  rise  of  pressure  in  all  the 
veins  below  the  point  of  constriction  but  insufficient  to  inter- 
fere appreciably  with  the  arterial  supply,  caused  no  diminution 
in  the  specific  gravity  of  the  tissuiss  for,  at  any  rate,  one  hour 
after  the  application  of  the  ligature.  We  can  however  pro- 
duce an  oedema  if  we  raise  the  intra-capillary  pressure  still 
higher  than  in  these  experiments.  According  to  Paschutin  f 
ligature   of   all   the   venous  trunks  of   the   dog's  leg  causes 


^=  Phil.  Trans.,  1894,  B.,  p.  779. 
t  Ludwig's  Arheiten,  1873,  p.  95. 


THE  CAUSATION  OF  DROPSY  159 

oedema  of  the  foot  and  ankle.  Eanvier  *  has  shown  that  if, 
after  hgature  of  the  inferior  vena  cava,  the  sciatic  nerve  be 
divided  on  one  side  so  as  to  produce  dilatation  of  arterioles 
on  that  side,  the  limb  in  ^Yhich  the  nerve  has  been  divided 
will  become  oedematous.  According  to  Cohnheim  oedema  may 
be  brought  about  by  injecting  the  veins  of  the  leg  with 
plaster  of  Paris.  We  see  then  that  we  can  produce  oedema 
in  a  limb  provided  we  raise  the  intra-capillary  pressure  to  a 
sufficiently  high  point.  If  only  one  or  two  veins  be  obstructed, 
the  outflow  by  the  collateral  circulation  is  sufficient  in  a 
healthy  animal  to  ward  off  any  oedema.  If  the  lymph  be  col- 
lected by  placing  a  cannula  in  one  of  the  lymphatics  of  the 
leg,  it  will  be  observed  that  after  these  severe  obstructions  it 
becomes  red  from  the  presence  of  red  blood  corpuscles.  In 
the  ordinary  oedema  of  venous  obstruction  in  man  the  lymph 
is  generally  perfectly  clear,  and  the  presence  of  red  corpuscles 
shows  that  the  rise  of  intra-capillary  blood  pressure  under 
these  circumstances  is,  so  to  speak,  hyper-physiological,  and 
is  probably  never  attained  under  ordinary  conditions  either 
of  health  or  disease.  Why  then  do  we  not  obtain  oedema  of 
the  dog's  leg  by  simple  ligature  of  the  vena  cava  or  femoral 
vein  ?  In  man  we  know  that  obstruction  of  either  of  these 
two  vessels  frequently  brings  about  oedema  of  the  lower 
extremities,  and  that  the  oedema  fluid  present  in  the  inter- 
stices of ,  the  tissues  is  colourless  and  free  from  red  blood 
corpuscles,  i.e.,  corresponds  to  the  lymph  of  moderate  venous 
obstruction.  The  apparent  discrepancy  which  is  found  here 
between  clinical  observations  and  the  results  of  experiment 
depends  on  the  fact  which  I  have  emphasised  at  the  begin- 
ning of  this  lecture,  namely,  that  it  is  impossible  to  upset 
the  physiological  balance,  which  prevents  the  occurrence  of 

*  Comptes  rendus,  LXIX.  1869. 


160  THE  FLUIDS  OF  THE  BODY 

dropsy,  by  a  moderate  disturbance  of  either  of  the  factors 
lymph  production  or  lymph  absorption.  Such  an  enormous 
rise  of  capillary  pressure,  as  is  produced  by  filling  all  the 
veins  of  the  leg  with  plaster  of  Paris,  probably  rarely  or 
never  occurs  under  clinical  conditions.  The  occurrence  of 
dropsy  in  man  in  consequence  of  venous  obstruction  is 
nearly  always  due  to  the  simultaneous  working  of  two  or 
more  factors.  We  have  therefore  to  decide  in  the  first  place 
why,  in  a  healthy  animal  with  a  moderate  venous  obstruc- 
tion, no  oedema  is  produced,  and  secondly  what  are  the 
subsidiary  factors  which  in  man  combine  with  the  venous 
obstruction  to  bring  about  an  oedema. 

In  considering  the  first  point,  it  is  essential  to  remember 
that  in  the  case  of  oedema  of  the  limbs  we  are  dealing  with 
the  most  impermeable  capillaries  in  the  body,  so  that  under 
normal  conditions  a  considerable  capillary  pressure  is  required 
to  separate  the  lymph  from  the  blood,  and  the  lymph  so 
separated  has  lost  the  greater  part  of  its  protein.  I  have 
already  shown  how,  in  consequence  of  this  difference  of  com- 
position between  plasma  and  lymph,  there  is  an  accurate 
balance  between  the  force  tending  to  produce  exudation — i.e., 
the  capillary  pressure — and  the  force  tending  to  produce 
absorption — i.e.,  the  difference  of  osmotic  pressures  between 
blood-plasma  and  lym|)h.  If  in  a  normal  animal  a  vein 
be  obstructed,  the  first  effect  is  a  rise  of  capillary  pressure 
and  increased  exudation.  Since  however  in  the  affected 
capillaries  and  veins  the  onward  flow  of  blood  is  checked,  the 
increased  exudation  must  be  at  the  expense  of  an  increased 
concentration  of  the  blood-plasma.  This  increase  in  concen- 
tration must  cause  an  increase  in  the  difference  between  the 
osmotic  pressures  of  plasma  and  lymph,  and  the  absorbing 
force  : — i.e.,  the  osmotic  pressure  of  the  plasma,  will  rise  until 
it  is  equal  to  the  driving-out  force — i.e.,  the  capillary  pressure. 


THE  CAUSATION  OF  DROPSY  161 

In  a  healthy  dog  with  normal  vessels  the  processes  tending  to 
cause  cedema  will  be  pulled  up  almost  as  soon  as  they  have 
started,  and  no  oedema  will  result  from  moderate  venous 
congestion.  It  is  easy  now  to  see  how  we  might  cause  oedema 
by  venous  congestion.  In  the  normal  animal  the  factor  which 
restrains  the  appearance  of  oedema  is  the  impermeability  of  the 
vessel  wall,  since  it  is  this  impermeability  which  maintains  the 
difference  in  osmotic  pressure  between  blood  and  lymph.  If 
we  can  increase  the  permeability  in  any  way,  the  balance 
of  processes  will  be  upset,  exudation  will  predominate  over 
absorption,  and  oedema  will  result.  One  method  by  which 
this  may  be  effected  is  that  of  scalding.  If  the  limb  of  an 
ansesthetised  animal  be  plunged  into  water  at  50°  or  60° 
and  kept  there  for  some  minutes,  it  is  found  that  not  only  is 
the  lymph  flow  from  the  limb  increased,  but  that  it  now 
reacts  immediately  to  changes  in  the  capillary  blood  j)ressure, 
any  rise  of  the  latter,  whether  occasioned  by  arterial  dilatation 
or  by  venous  obstruction,  causing  immediately  a  great 
increase  in  the  lymph  flow  from  the  limb.  Moreover  the 
lymph  obtained  under  these  circumstances  is  found  to  be 
more  concentrated  than  that  normally  flowing  from  the  limb, 
showing  that  the  permeability  of  the  capillary  wall  has  been 
increased.  It  must  be  remembered  that  the  capillary  wall 
is  alive  and  is  composed  of  cells  which  have  a  metabolism 
of  their  own,  and  which,  like  all  other  cells  of  the  body,  are 
dependent  for  their  proper  nutrition  on  a  free  supply  of 
oxygen  and  nutrient  material  and  a  free  exit  for  their  waste 
products.  Their  only  function,  so  far  as  we  know,  is  the 
maintenance  of  their  integrity  as  a  membrane  with  certain 
properties  differing  according  to  the  region  of  the  body  in 
which  they  happen  to  be  situated.  If  they  are  injured  in  any 
way,  the  resistance  of  the  membrane  is  diminished  and  its 
permeability  is  increased.     Such  an  injury  will  follow  if  they 

F.B.  M 


162  THE  FLUIDS  OF  THE  BODY 

be  deprived  for  some   time   of   a   fresh   supply  of  nutrient 
material  and  oxygen.      Cohnheim  showed  that,   after   long- 
continued  anaemia  of  the  rabbit's  ear,  the  vessels  became  so 
permeable  that  the  restoration  of  the  normal  circulation  was 
followed  by  pronounced  oedema   of   all  the  tissues.     If  the 
anaemia   be   of    shorter  duration,   no   oedema   is   caused   by 
restoration  of  the  normal  circulation,  but  can  be  called  forth 
at  once  by  ligaturing  the  principal  vein  draining  the  part. 
In  the  same  way  Lazarus  Barlow  found  that  if  a  limb  had 
been    deprived   of   blood   altogether   for   an  hour,   on   then 
admitting  the  circulation  there  was  a  marked  increase  in  the 
amount  of  tissue  fluid,  and  this  increase  was  still  more  pro- 
nounced if  the  veins  of  the  limb  were  constricted.     Now  a 
long-continued  venous  obstruction  must  affect  the  vessel  walls 
in  the  same  way  as  anaemia,  since  here  also  the  cells  will  be 
starved  or  asphyxiated.      Hence  it  is  that,  in  the  chronic  con- 
ditions which  give  rise  to  venous  obstruction  in  man,  we  have 
the  production  of  oedema.      Moreover,  in  man  when  dropsy 
occurs  as  the  result  of  venous  obstruction,  there  are  generally 
other  conditions  present  which  tend  to  damage  the  vessel  wall 
and  so  increase  its  permeability.     Thus  the  mere  presence  of 
thrombosis  points  to  a  probable  defective  nutrition  of  the  vas- 
cular endothelium,  and  is  found  most  frequently  in  patients 
suffering  from  anaemia  or  allied  changes  in  the  blood.     The 
occurrence  of  malignant  growths  in  the  neighbourhood  of  a  vein 
is  usually  associated  with  a  condition  of  cachexia,  and  there- 
fore with  an  impoverished  blood  supply  to  the  endothelium. 
We  have  experimental  evidence  that  the  circulation  of  watery 
blood  through  the  vessels,  if  continued  for  some  length  of 
time,  alters  the  vessel  wall  to  such  an  extent  that  a  moderate 
venous  obstruction  will  produce  oedema.    Cohnheim  has  shown 
that,  although  ligature  of  the  femoral  vein  causes  no  oedema 
in  a  healthy  dog,  it  will  do  so  if  the  animal  be  first  rendered 


THE    CAUSATION    OF    DROPSY  163 

hydraemic  by  bleeding  repeatedly  at  intervals  of  a  few  days. 
It  must  be  remembered  that  in  this  case  we  have  still  a  third 
factor  which  helps  in  the  production  of  oedema.  A  more 
watery  plasma  will  filter  more  easily  through  the  vessel  wall, 
and  the  diminution  of  proteins  in  the  plasma  must  be  accom- 
panied by  a  diminution  of  the  osmotic  pressure  in  the  plasma, 
which  is  active  in  absorption.  To  sum  up,  we  may  say  that 
oedema  can  never  be  brought  about  in  the  limbs  by  a  moderate 
rise  of  venous  pressure,  provided  that  the  capillaries  retain 
their  normal  impermeability.  CEdema  will  occur  as  soon  as 
the  iDermeability  of  the  vessels  is  increased.  The  injury 
leading  to  this  increase  in  permeability  may  be  brought 
about  in  any  of  the  following  ways :  (1)  long-continued 
venous  congestion  (asphyxia  of  cells) ;  (2)  an  excessive  rise  of 
intra-capillary  pressure  breaking  down  the  normal  resistance 
of  the  cells  ;  and  (3)  malnutrition  due  to  an  impoverished 
state  of  the  blood. 

The  relative  importance  of  these  three  factors  is  well  brought 
out  in  some  recent  experiments  by  Bolton.*  This  observer 
devised  a  very  ingenious  method  for  causing  any  degree  of 
obstruction  of  the  big  venous  trunks,  i.e.,  the  superior  vena 
cava,  or  inferior  vena  cava,  or  the  portal  vein.  We  shall 
have  occasion  directly  to  turn  to  the  bearings  of  his  experi- 
ments on  the  causation  of  the  dropsy  which  occurs  in  heart 
disease,  but  we  may  consider  here  shortly  the  results  obtained 
by  him  on  constriction  of  the  superior  cava.  The  constric- 
tion was  effected  by  encircling  the  vein  with  a  split  segment 
of  a  gum  elastic  catheter,  which  was  bound  round  the  vein. 
By  this  means  it  was  possible  to  occlude  the  vein  completely 
or  to  diminish  its  lumen  to  any  desired  extent.     He  found 

^  Cliaiies  Bolton,  "On  the  Pathology  of  the  Dropsy  produced  by 
Obstruction  of  the  Superior  and  Inferior  Venae  Cavse  and  the  Portal 
Vein,"  Proc.  Eoy.  Soc.  B.,  Vol.  LXXIX.,  1907,  p.  267. 

M   2 


164  .  THE  FLUIDS  OF  THE  BODY 

that  in  every  case  where  the  lumen  was  diminished  to  three- 
fifths  of  the  normal  amount,  i,e.,  sufficient  to  cause  an 
appreciable  rise  of  pressure  in  the  jugular  vein,  oedema  was 
produced  within  one  or  two  days.  The  oedema  affected  the 
superior  mediastinum,  the  tissues  of  the  neck,  and  in  most 
cases,  owing  to  the  drainage  of  the  fluid  from  the  mediastinal 
tissues  into  the  pleural  cavities,  there  was  hydrothorax  on 
both  sides.  The  effects  were  more  marked  when  the  obstruc. 
tion  was  placed  below  the  azygos  vein,  i.e.,  between  this  vein 
and  the  heart.  Since  the  obstruction  was  always  followed  by 
a  rise  of  venous  pressure  in  the  jugular  vein  and  by  a 
distension  of  all  the  veins  of  the  neck,  it  might  be  thought 
that  the  experiment  afforded  a  striking  confirmation  of  the 
important  part  played  by  rise  of  pressure  in  the  production  of 
dropsy ;  but  Bolton  found  that,  if  the  venous  pressure  in 
the  jugular  vein  were  measured  a  few  hours  after  the  obstruc- 
tion had  been  produced,  although  the  veins  were  still  dis- 
tended, the  pressure  in  them  had  fallen  to  a  point  that  was 
approximately  normal.  The  only  mechanical  change  present 
therefore  was  a  stagnation  of  the  blood  in  dilated  veins. 
Although  at  the  point  of  obstruction  itself,  owing  to  the 
stagnation  and  the  consequent  absence  of  fall  of  pressure 
from  periphery  to  centre,  the  pressure  would  be  somewhat 
above  normal,  Bolton  is  justified  in  concluding  that  there 
can  be  no  appreciable  rise  of  pressure  in  the  capillaries  which 
are  responsible  for  the  increased  transudation.  Yet  this 
increased  transudation  and  the  production  of  dropsy  is  pro- 
ceeding rapidly  at  a  time  when  the  pressures  have  fallen,  and 
one  is  therefore  driven  to  the  conclusion  that  the  essential 
factor  here  is  not  rise  of  pressure,  but  the  alteration  of  the 
vessel  wall  consequent  on  stagnation  of  blood  and  privation  of 
oxygen.  The  alteration  in  the  muscular  tissue  of  the  veins  is 
shown  by  the  fact  that  they  are  distended  to  a  large  extent 


THE    CAUSATION    OF    DROPSY  165 

under  a  normal  pressure.  The  alteration  in  the  endothelium  of 
the  capillary  wall  must  be  regarded  as  the  essential  factor  in 
the  production  of  the  cedema.  It  is  possible  that  the  mal- 
nutrition of  the  extra-vascular  tissues  may  also  play  some  part 
in  the  production  of  oedema,  e.g.,  by  the  production  of 
injurious  disintegrative  products  or  by  disorganisation  of  the 
elastic  framework  of  the  tissue  spaces. 

Much  more  frequent  than  the  oedema  due  to  local  venous 
obstruction  is  the  oedema  which  occurs  as  a  consequence  of 
uncompensated  or  imperfectly  compensated  heart  disease.  In 
this  class  of  cases  we  have  much  more  complicated  conditions 
than  in  the  class  I  have  just  discussed.  The  oedema  of  heart 
disease  is  generally  looked  upon  as  obviously  due  to  a  rise  in 
venous  pressure  and  consequent  venous  obstruction.  Taking 
the  existence  of  a  high  pressure  on  the  venous  side  of  the 
heart  in  such  cases  as  a  fact,  we  have  to  inquire  into  the 
causes  for  this  rise  of  pressure  and  whether  this  rise  of 
pressure  will  extend  to  the  capillaries.  To  investigate  the 
causation  of  the  dropsy  in  heart  disease  therefore,  we  must 
take  into  account  the  alterations  in  the  circulation  as  well  as 
the  alterations  in  the  absorption  and  production  of  lymph. 
The  vascular  system  in  an  animal  can  be  looked  upon  as  a 
closed  system  of  tubes  having  a  definite  capacity.  If  the 
circulation  were  brought  to  a  standstill,  the  pressure  at  all 
parts  of  the  system  would  become  the  same.  This  pressure  is 
called  the  mean  systemic  pressure,  and  in  a  dog  is  equal  to 
about  10  mm.  Hg.  Now  in  such  a  system  it  is  evident  that 
the  height  of  this  mean  pressure  depends  solely  on  the 
relation  between  the  amount  of  contained  fluid  and  the 
capacity  of  the  system.  If  circulation  be  established  by 
means  of  the  heart's  beat,  the  relation  between  the  capacity 
and  the  volume  of  blood  remaining  unchanged,  no  alteration 
can  occur  in  the  mean  pressure.     All  we  have  is  an  alteration 


166  THE  FLUIDS  OF  THE  BODY 

in  the  distribution  of  the  pressure.  Behind  the  heart — that 
is  to  saj^,  on  its  venous  side — the  pressure  will  sink  below  the 
mean  systemic  pressure ;  on  the  arterial  side  the  pressure  will 
be  raised  above  the  mean  pressure.  If  after  the  establishment 
of  the  circulation  the  action  of  the  heart-pump  be  interfered 
with,  as  by  damage  to  the  valves,  or  be  checked  altogether, 
the  pressures  on  each  side  will  tend  to  return  to  the  zero  of 
the  system — i.e.,  the  mean  systemic  pressure.  As  a  result 
there  will  be  a  fall  of  arterial  pressure  and  a  rise  of  venous 
pressure  to  this  point.  It  becomes  important  to  know  at 
what  point  in  the  system  the  pressure,  while  the  circulation 
is  going  on,  is  equal  to  the  mean  systemic  pressure. 

In  a  series  of  experiments  which  I  carried  out  many  years 
ago  with  W.  M.  Bayliss  *  we  came  to  the  conclusion  that  this 
turning  point  of  the  circulation,  so  to  speak,  is  situated  in  the 
region  of  the  hepatic  capillaries  in  the  abdomen  and  at  about 
the  level  of  Poupart's  ligament  in  the  femoral  vein.  Failure  of 
the  heart-pump  would  cause  a  rise  of  pressure  in  the  vena  cava 
and  in  the  large  veins  of  the  neck,  but  a  fall  of  pressure  in  the 
portal  vein,  in  the  peripheral  veins  of  the  legs,  as  well  as 
in  the  arteries.  It  would  seem  therefore  that  failure  of  the 
heart's  action,  to  whatever  cause  it  may  be  due,  can  only 
bring  about  a  fall  of  pressure  in  the  capillaries  of  the 
intestines  and  peripheral  parts  of  the  body.  Any  general 
constriction  of  the  arterioles  would,  however,  raise  the  mean 
systemic  pressure,  so  that  failure  of  the  heart,  if  it  were 
followed  by  constriction  of  the  arterioles,  would  cause  a  rise 
of  pressure  above  normal  which  might  extend  as  far  as  the 
peripheral  end  of  the  veins  of  the  leg.  Bolton,  as  a  matter  of 
fact,  has  found  a  distinct  rise  of  pressure  in  the  veins  of  the 
foot  as  a  result  of  interference  with  the  action  of  the  heart  so 

*  Bayliss  and  Starling,  Journ.  of  Physiol,  XVI.,  159,  1894. 


THE  CAUSATION  OF  DROPSY  167 

as  to  imitate  the  condition  which  is  present  in  faikire  of 
com^Densation.  There  can  be  no  doubt  that  this  rise  of  venous 
pressure  would  be  aided  by  the  condition  of  plethora  which, 
as  I  have  shown  in  my  last  lecture,  is  probably  an  almost 
invariable  concomitant  of  chronic  failure  of  compensation.  It 
seems  very  doubtful,  however,  if  not  absolutely  disproved,  that, 
even  in  marked  cases  of  failure  of  compensation,  one  is  justi- 
fied in  predicating  a  rise  of  pressure  in  the  capillaries  of  the 
body  above  its  normal  extent.  Indeed,  it  results  from  Bolton's 
experiments  on  this  subject  that  oedema  may  occur  under 
conditions  in  which  the  capillary  pressure  is  certainly  not 
higher  than  in  the  normal  animal.  Bolton  imitated  the  con- 
ditions in  failure  of  compensation  in  two  ways.  In  the  first 
series  of  experiments  he  interfered  with  the  diastolic  dilata- 
tion of  the  heart  by  constricting  the  pericardium  by  means 
of  ligatures.*  In  a  large  number  of  cases  he  obtained  survival 
of  the  animal  and  the  production  of  ascites,  i.e.,  accumulation 
of  fluid  in  the  abdominal  cavity.  In  another  series  of  experi- 
ments Bolton  caused  a  simultaneous  constriction  of  the  superior 
cava  and  of  the  inferior  cava,  the  former  being  constricted  by 
means  of  a  catheter  to  three-fifths  of  its  normal  dimensions, 
and  the  latter  also  to  two-thirds. 

The  results  obtained  are  of  such  importance  for  the  under- 
standing of  the  conditions  in  heart  disease,  that  some  of  the 
experiments  may  be  here  quoted. 

In  the  following  experiment  the  effects  of  constriction  of 

the  pericardium  on  the  arterial  and  venous   pressures  were 

observed : — 

Cat.  Weight  3,000  grams.  Anaesthetised  with  ether ;  tracheotomy  and 
artificial  respiration.      Cannula   in  right  femoral  artery;    cannula  also 

*  C.  Bolton,  "The  Experimental  Production  of  Uncompensated 
Heart  Disease,  with  especial  Eeference  to  the  Pathology  of  Dropsy," 
Journ.  of  Pathology,  IX.,  67,  1903. 


168 


THE    FLUIDS    OF    THE    BODY 


introduced  into  a  brancL.  of  the  left  femoral  vein,  just  above  the  foot,  and 
pushed  down  till  it  just  reached  the  opening  of  the  branch  into  the  main 
trunk. 

Pressures  at  beginning  of  the  operation : — 

Artery.  Vein. 

110  mm.  Hg 140  mm.  MgS04  solution. 

1.  Pericardium  constricted  ivith  Forceps. 
The  pressures  at  once  altered  as  follows,  the  presystolic  pulsation  in  the 
vein,  together  with  the  rises  in  pressure  synchronous  with  insufflation  of 
the  lungs  being  very  evident : — 


\rtery. 

Vein. 

.     50 

mm.  Hg. 

175 

mm. 

MgS04 

solution. 

In    5 

minutes 

.  .     50 

160 

,,     5 

.     40 

155 

„  10 

.     48 

150 

>.     5 

.     60 

148 

„     5 

.     70 

150 

„     5 

.     78 

146 

35 

2.  Pericardium  further  constricted. 
Artery.  Vein. 

. .     60  mm.  Hg.  164  mm.  MgSOi  solution. 

In    5  minutes  . .     60         ,,  155  ,,  ,, 

„     o       „  ..70         „  148 

,,     5       ,,  .  .      /O         ,,  143  ,,  ,, 


15 


In    5 
„  10 

15 


3.  Pericardium  constricted  still  further. 

Artery.  Vein. 

. .     50  mm,  Hg.     150  mm.  MgS04  solution, 
minutes  . .     48         ,,  145  ,,  ,, 

,,  ..     50         ,,       .    140 


The  pericardium  was  now  released,  and  at  once  the  pressures  became— 

Artery.  Vein. 

80  mm.  Hg.     100  mm.  MgS04  solution. 

In    3  minutes     ..      80 — 90       ,,  95  ,,  No  venous 

"  "  "       pulse. 

„     5       „  ..     90-100    „  85 


THE    CAUSATION    OF    DROPSY 


169 


In    5  minutes 
„  30       „ 

»>  15       ,, 


4.  Pericardium  again  constricted. 

Artery.  Vein. 

. .     40  mm.  Hg.     120  mm.  MgSO^  solution. 
50         ,.  150 


1  hour 


50 
46 
50 
52 


130 
123 
130 
130 


The  pericardium  was  now  released,  and  at  once  the  pressures  became — 


Ai'tery. 
80  mm.  Hg. 


Vein. 

80  mm.  MgS04  solution. 


This  experiment  shows  that,  although  there  is  a  rise  of 
pressure  in  the  femoral  vein  synchronous  with  the  fall  of 
arterial  pressure,  the  venous  pressure  subsequently  falls  to  its 
normal  level  in  the  course  of  an  hour  or  so.  This  fall  of 
venous  pressure  is  not  due  to  gradual  stretching  of  the 
pericardium,  since  the  arterial  pressure  remains  at  the  low 
level  to  which  it  was  reduced  by  the  constriction. 

Similar  results  were  obtained  by  obstructing  the  superior 
together  with  the  inferior  vena  cava.  Thus  on  completely 
ligaturing  the  superior  cava  and  constricting  the  inferior  cava 
to  a  diameter  of  3  mm.  the  arterial  pressure  fell  considerably, 
while  the  venous  pressure  rose.  In  a  few  hours  the  venous 
pressures,  taken  in  the  peripheral  ends  of  the  jugular  and 
femoral  veins,  often  fell  to  normal.  In  every  case  however 
dropsy  was  produced,  fluid  being  found  a  few  days  later 
in  each  pleural  cavity,  in  the  peritoneal  cavity,  and  in  the 
mediastinum.  It  is  especially  important  to  note  that  the 
dropsy  was  produced  at  a  time  when  the  venous  pressures  had 
fallen  to  normal. 

The  effects  of  constriction  of  the  inferior  cava  on  the  blood 


170  THE  FLUIDS  OF  THE  BODY 

pressure  m  different   parts  of   the   body  may,  according  to 
Bolton,  be  summed  up  as  follows : — 

Immediate  Result : — 

Else  of  pressure  in  capillaries  of  trunk. 

,,  ,,         ,,  ,,  ,,  leet. 

Fall  of  pressure  in  capillaries  of  head. 
, ,  , ,         , ,  all  arteries  of  body. 

Result  in  1 — 1^  hours  : — 
Trunk  and  feet  normal. 
Head  below  normal. 
Arterial  pressure  below  normal. 

Later : — 

Trunk  normal  or  raised. 

Feet  below  normal  or  normal. 

Head  below  normal. 

Arterial  pressure  below  or  normal. 

This  observer  regards  the  later  rise  of  venous  pressure  in  con- 
gested area  and  in  arteries  as  dependent  entirely  on  vaso-con- 
striction,  and  not  on  absorption  of  fluid,  though  he  himself 
shows  that  there  is  an  absorption  of  fluid  in  the  areas  of 
low  pressure  to  replace  that  lost  as  dropsy  in  the  congested 
areas.  I  am  still  inclined  to  think  that  both  factors  play  an 
important  part  in  the  production  of  the  comjDlex  of  symptoms 
observed  in  failure  of  compensation.  Bolton's  results  show 
clearly  that  a  condition  of  plethora  or  of  raised  capillary 
pressure  are  neither  of  them  necessary  for  the  production  of 
oedema.  It  may  be  noted  that  in  all  the  experiments  the 
veins  were  dilated  so  long  as  the  increased  transudation  was. 
occurring.  The  pressures,  however,  in  the  j)eripheral  parts  of 
the  veins,  i.e.,  in  the  jugular  vein  and  in  the  femoral  vein^ 
varied  within  normal  limits.  The  venous  wall  was  therefore 
altered  so  as  to  dilate  abnormally  under  pressures  which  were 
normal.  Since  the  arterial  pressure  was  either  subnormal  or 
normal,  we  have  no  grounds  for  assuming  that  there  was  any 
rise  of  capillary  pressure  to  account  for  the  production  of  the 


THE    CAUSATION    OF    DROPSY  171 

oedema ;  the  essential  factor  here,  as  in  the  case  of  obstruc- 
tion of  a  vein,  is  stagnation  of  the  blood.  There  is  from  these 
capillaries  an  increased  transudation  under  normal  pressure : 
that  is  to  say,  the  permeability  of  the  capillary  endothelium 
is  altered  as  a  result  of  defective  nutrition. 

In  heart  disease  a  fact  is  present  which  is  not  operative  in 
simple  venous  obstruction,  namely  a  hindrance  to  the  outflow 
by  the  lymphatics  in  consequence  of  the  rise  of  pressure  and 
stagnation  of  the  blood  in  the  superior  vena  cava  near  the 
heart.  The  same  rise  of  pressure,  which  we  must  assume  to 
be  confined  to  the  big  veins  in  the  immediate  neighbourhood 
of  the  heart,  will  probably  cause  a  rise  of  capillary  pressure  in 
the  liver,  and  this  is  seen  in  the  swelling  and  pulsation  of  this 
organ  which  is  a  constant  result  of  failure  of  the  normal 
pumping  action  of  the  right  heart.  The  flow  of  lymph  from 
this  organ  must  therefore  be  largely  increased,  and  probably 
this  liver  lymph  contributes  appreciably  to  the  production  of 
ascites,  which  is  one  of  the  earliest  jDhenomena  following 
failure  of  the  heart's  action.  The  production  of  dropsy  in 
heart  disease  is  thus  by  no  means  simple.  It  involves  a 
complicated  series  of  interacting  mechanisms,  all  of  which 
tend  to  the  death  of  the  organism.  We  may  sum  up  the 
sequence  of  events  which  ensue  on  failure  of  compensation  as 
follow^s  : — 

Stage  I.--Heart-pump  failure  ;  fall  of  arterial  pressure 
and  rise  of  pressure  in  the  venous  trunks ;  fall  of  capillary 
pressure  in  the  peripheral  parts  of  the  body,  in  the  kidneys, 
cind  in  the  intestine. 

Stage  II. — The  organism  attempts  to  keep  up  the  arterial 
pressure,  which  determines  the  blood  supply  to  the  brain,  by 
constriction  of  the  arterioles.  Arterial  pressure  is  thus  raised 
to  a  certain  degree  ;  the  venous  pressure  is  raised  still  higher 
than  before,  so  that  the  rise  extends  to  the  venous  radicles  in 


172  THE  FLriDS  OF  THE  BODY 

the  tissues.  It  is  doubtful  whether  there  is  any  actual  rise  of 
capillary  pressure. 

Stage  III. — By  the  dilatation  of  the  veuis  the  venous 
pressure  tends  to  sink.  The  inadequate  filling  of  the  arterial 
system  calls  forth  an  increased  intake  of  fluid  into  the  blood. 
We  therefore  get  a  series  of  conditions  tending  to  increase  the 
blood  fluid  at  the  expense  of  the  tissue  fluid  and  a  continual 
effort  by  a  rise  of  venous  pressure  to  stimulate  the  failing 
heart  so  that  it  can  pump  sufficient  blood  into  the  contracted 
arterioles. 

Stage  IF.— Before  however  any  large  alteration  in  the 
total  volume  of  blood  has  time  to  take  place,  the  capillary 
walls  begia  to  suffer  from  the  stagnation  of  the  blood  conse- 
quent on  the  failure  of  the  heart-pump.  Wherever,  therefore, 
the  normal  pressure  in  the  capillaries  due  to  the  heart  is  raised 
by  hydrostatic  pressure  due  to  gravity,  there  is  an  increased 
transudation  and  an  acetmiulation  of  fluid  in  the  connective 
tissues.  In  the  animal  at  rest  the  first  sign  of  increased 
transudation  occurs  in  the  abdominal  organs,  especially  in 
the  liver.  Xext  we  get  the  increased  transudation  in  the 
mediastinal  tissues.  In  man,  with  the  assumption  of  the 
erect  position,  the  pressure  of  the  blood  on  these  capillaries 
is  relieved  at  the  expense  of  those  of  the  lower  part  of  the 
body  and  legs,  so  that  there  is  diminution  of  the  hydrothorax 
and  ascites,  but  production  of  oedema  in  the  lower  extremities. 

In  both  these  classes  of  dropsy  therefore,  the  primary 
factor  is  an  alteration  in  the  mechanical  conditions  of  the 
circulation.  As  a  result  there  is  altered  nutrition  of  the 
capiUary  wall,  increased  permeability,  and  production  of 
dropsy. 

In  the  next  class  with  which  we  have  to  deal,  the  primary 
change  affects,  not  the  mechanical  conditions  of  the  circulation, 
but  the  vessel  wall.    A  change  of  the  filtering  membrane  is  thus 


THE  CAUSATION  OF  DROPSY  173 

produced,  so  that  it  becomes  more  permeable,  and  allows, 
under  normal  capillary  pressures,  an  excessive  exudation,  and 
the  exudation  is  richer  in  protein  than  is  the  normal  lymph  of 
the  region  in  question.  Since  an  alteration  of  the  vessel  wall  is 
one  of  the  main  features  of  inflammation,  Cohnheim  has  classed 
all  oedemas,  in  which  the  primary  affection  is  that  of  the  vessel 
wall,  as  inflammatory  oedemas.  I  have  already  pointed  out 
various  means  by  which  the  permeability  of  the  capillary  wall 
might  be  increased,  and  showed  how,  under  these  circum- 
stances, the  limb  capillaries  might  be  reduced  to  the  condition 
of  liver  capillaries.  Here,  as  in  all  other  cases  in  which 
oedema  occurs,  we  have  more  than  one  factor  at  work.  The 
capillary  pressure  of  the  part  remaining  at  its  normal  height, 
the  increased  permeability  allows  of  a  largely  increased  exuda- 
tion—  there  is  increased  lymph  production.  The  lymph 
however  contains  more  proteins  than  normal,  so  that  the 
difference  of  osmotic  pressure  between  it  and  the  circulating 
plasma  is  diminished,  thereby  causing  a  diminution  of  the 
absorbing  force.  In  all  cases  of  inflammatory  oedema  these 
two  factors  are  at  work  concurrently :  increased  production 
and  diminished  absorption.  This  alteration  of  the  vessel 
wall  may  be  brought  about  in  two  ways,  either  by  the  appli- 
cation of  injurious  agents  to  the  vessels  of  any  given  part,  or 
by  the  introduction  of  poisonous  substances  into  the  blood 
stream.  Thus  a  local  alteration  of  the  vessel  wall  may  be 
caused  by  application  of  mechanical  violence,  crushing  the 
tissues.  It  is  possible  that  in  this  case  we  have  at  work,  not 
only  the  direct  result  of  the  injury  on  the  vessel  wall,  but 
also  a  secondary  injury  of  the  capillaries  in  consequence  of 
the  development  of  poisonous  products  of  disintegration  in 
the  bruised  tissues  surrounding  the  capillaries.  We  can  pro- 
duce the  same  change  by  exposing  the  tissues  for  a  few 
minutes  to  a  temperature  of  over  50°  C,  or  by  depriving  them 


174  THE  FLUIDS  OF  THE  BODY 

for  some  time  of  the  normal  blood-flow.  All  the  local  oedemas 
produced  by  inoculation  of  chemical  or  microbic  poisons  at 
the  point  of  inoculation  are  of  this  nature.  The  swelling 
produced  by  the  sting  of  a  bee.  or  by  the  inoculation  of 
anthrax,  is  due  to  the  deleterious  effects  of  the  poison  on 
the  capillar}^  walls  at  the  point  of  inoculation.  Metchni- 
koff  showed  that  the  emigration  of  white  blood  corpuscles 
occurring  in  inflammation  is  to  be  looked  upon  as  a  physio- 
logical reaction  of  the  organism  directed  to  its  preservation, 
and  it  seems  probable  that  the  salutary  import  of  this  pro- 
cess may  also  hold  good  for  the  local  oedema.  As  the  result 
of  the  injury  of  the  capillary  walls,  a  more  concentrated 
lymph  is  poured  out,  i.e.,  a  lymph  containing  more  proteins 
to  serve  for  the  nutrition  of  the  cells  of  the  part.  Whether 
or  not  this  is  the  case,  the  j)resence  of  this  concentrated 
lymph  must  be  of  great  use  to  the  organism  in  the  regenera- 
tion of  tissue  which  follows  on  inflammation. 

We  know  less  clinically  of  the  cases  in  which  the  injury  to 
the  vessel  wall  is  brought  about  by  a  poison  circulating  in 
the  blood.  I  have  already  described  to  you  the  class  of 
animal  poisons  which  were  grouped  together  by  Heidenhain 
as  his  first  class  of  lymph agogues.  The  chief  action  of  these 
bodies  is  on  the  capillaries  of  the  liver.  Their  action,  how- 
ever, is  not  absolutely  confined  to  this  organ.  I  have 
experimental  evidence  that  there  is  a  certain  degree  of 
increased  permeability  of  the  intestinal  capillaries  after  the 
injection  of  these  bodies — an  increased  permeability  which 
is  brought  into  evidence  only  after  raising  to  a  certain  extent 
the  pressure  in  these  capillaries.  These  bodies,  however, 
can  also  affect  the  capillaries  of  the  skin.  In  a  number  of 
the  ex2)eriments  in  which  these  bodies  have  been  injected, 
we  may  observe  a  rapid  development  of  an  urticarial  eruption 
on  the  skin,  and  you  are  all  familiar  with  the  fact  that  the 


THE    CAUSATION    OF    DROPSY  175 

ingestion  of  the  animals  from  which  these  bodies  are  derived 
(mussels,  crayfish,  lobster)  is  often  followed  in  man  by  an 
eruption  of  urticaria,  which  may  or  may  not  be  accompanied 
by  other  symptoms  of  poisoning.  The  sudden  onset  of  urti- 
caria and  similar  eruptions  in  man,  combined  with  the  fact 
that  their  distribution  may  correspond  with  that  of  a  certain 
nerve,  has  given  rise  to  the  supposition  that  these  oedemas 
may  be  nervous  in  origin :  that,  in  fact,  we  have  an 
increased  production  of  lymph  under  the  direct  influence  of 
the  nervous  system.  If  lymph  were  to  be  looked  upon  as  a 
secretion,  we  should  expect,  from  analogy  with  other  secre- 
tions, to  find  it  subject  to  the  central  nervous  system,  and  at 
one  time  I  made  diligent  search  for  direct  evidence  of  the 
influence  of  the  nervous  system  on  lymj^h  formation.  The 
results  of  my  experiments  were  however  opposed  to  such  an 
hypothesis.  In  every  case  where  nerve  section  or  nerve 
excitation  gave  rise  to  increased  lymph  production  in  any 
part,  I  found  that  the  increase  was  due  primarily  to  a  rise 
of  capillary  pressure  in  the  part,  and  was  therefore  only 
a  secondary  effect  of  the  interference  with  the  nerve. 
The  best-marked  case  of  so-called  nervous  oedema  is  the 
unilateral  oedema  of  the  tongue,  which  may  be  produced 
by  stimulating  one  lingual  nerve.  The  stimulation  of  the 
lingual  nerve  causes  extreme  vaso-dilatation  of  the  vessels 
of  the  tongue,  and  the  increased  lymph  production  in  the 
tongue  is  evidently  the  direct  result  of  this  vaso-dilata- 
tion and  consequently  increased  capillary  pressure.  Here,  as 
in  all  other  cases  where  one  wishes  to  produce  oedema,  one 
must  not  rely  simply  upon  one  factor.  In  the  majority  of 
cases  the  oedema  produced  by  stimulating  the  lingual  nerve, 
i.e.,  by  a  simple  rise  of  capillary  pressure,  is  but  slightly 
marked.  One  can  however  produce  a  very  fine  oedema  of 
the  tongue  if  one  aids  the  filtration  process  and  diminishes 


176  THE  FLUIDS  OF  THE  BODY 

the  forces  tending  to  absorption  by  the  injection  of  a  large 
amount  of  normal  saline  solution  into  the  circulation.  I 
believe  that  all  cases  of  so-called  nervous  oedema  can  be 
explained  by  the  circulation  of  some  lymphagogue  substance 
in  the  blood  combined  with  local  vaso-dilatation,  which  may 
often  be  hysterical  or  central  in  origin.  More  evidence  is, 
however,  required  on  this  point  before  we  can  claim  to 
thoroughly  understand  the  causation  of  the  so-called  angio- 
neurotic oedemas. 

One  of  the  most  important  forms  of  dropsy,  i.e.,  that  which 
accompanies  renal  disease,  was  placed  by  Cohnheim  in  the 
category  of  inflammatory  dropsies.  One  objection  to  this 
view  is  afforded  by  the  fact  that  in  the  dropsy  of  Bright's 
disease  we  obtain  an  cedema  fluid  which  is  less  concentrated 
than  that  found  under  any  other  circumstances,  whereas  in 
the  changes  in  the  capillary  endothelium  brought  about  by 
inflammation  there  is  always  an  increased  permeability  of 
this  endothelium,  and  therefore  an  increased  amount  of 
protein  in  the  tissue  fluid  and  lymph.  Although  in  Bright's 
disease  the  blood-plasma  may  also  be  more  dilute  than 
normal,  the  diminution  in  its  concentration  does  not  seem 
sufficient  to  account  for  the  very  low  protein  content  to  be 
observed  in  the  oedema  fluid  of  the  same  disease.  The  dis- 
covery of  lymphagogues  naturally  suggested  that  the  change 
in  the  vascular  endothelium  in  Bright's  disease,  which  was 
assumed  to  be  responsible  for  this  increased  permeability, 
was  due  to  the  circulation  in  the  blood  of  some  poisonous 
substance  belonging  to  this  group  of  bodies,  and  lymphagogue 
effects  have  been  obtained  in  the  dog  on  the  intravenous 
injection  of  blood  serum  derived  from  an  ursemic  patient. 
Here  too  however,  if  we  were  dealing  with  increased  perme- 
ability, we  should  expect  to  find  a  raised  protein  content  in 
the  oedemic  fluid.     At  the  present  time  it  is  impossible  for  us 


THE    CAUSATION    OF    DROPSY  177 

to  come  to  any  conclusion  as  to  the  causation  of  the  oedema 
of  renal  disease,  though  it  seems  probable  that  the  causation 
is  to  be  sought  rather  along  the  lines  indicated  in  my  last 
lecture,  i.e.,  by  the  accumulation  of  substances  of  low  molecular 
weight  in  the  tissues  and  the  osmotic  attraction  of  fluid  by 
their  means,  than  as  a  result  of  an  increased  permeability 
of  the  vessel  wall  similar  to  that  found  in  inflammatory 
conditions. 

This  cursory  examination  of  the  alterations  in  physiological 
conditions  present  in  the  various  forms  of  dropsy  brings  to 
light  one  important  fact,  a  fact  on  which  much  stress  has 
already  been  laid  by  Cohnheim.     In  all  cases  the  primary 
cause  of  oedema  is  an  increased  transudation.     The  normal 
mechanism  of  absorption  may  for  some  time  hold  this  process 
in  check,  but  whenever  the  increased  exudation  endures  any 
length  of  time,  subsidiary  events  cause  a  breakdown  of  the 
absorbing  mechanism   and   the  occurrence   of   oedema.     On 
the  other  hand,  we  know  of  very  few  cases  in  which  oedema 
can  be  ascribed  primarily  to  a  diminished  absorption.  Obstruc- 
tion of  the  lymphatics  can  rarely  occur,  owing  to  the  multi- 
tudinous anastomoses  of  these   canals.      When   a  complete 
obstruction  does  take  place,  the  result  seems  to  be   rather 
a    general    hypertrophy   of   the    connective    tissues,   as    in 
elephantiasis,   than   a   true   oedema.     In   all   cases  however 
where  we  find  dropsy,  we  may  say  that,  in  addition  to  the 
primary  increased  exudation,  there  is  a  derangement  of  some 
part  of  the  absorbing  mechanism. 


F.B.  N 


INDEX 


Absorption  by  blood-vessels,  89. 

by  Ij^mpbatics,  88. 

dependence  on  diffusi- 

bility,  46. 

effected  by  osmotic  pres- 

sure of  proteins,  101. 

from  peritoneum,  49. 

from  serous  cavities,  90. 

from  tissue  spaces,  93. 

in  renal  tubules,  126. 

• mechanism  of,  97. 

■ ■       of  interstitial  fluids,  88 

—103. 

of  salts,  53. 

of  serum,  55,  102. 

of  sugars,  32,  60. 

of     tissue     fluid     after 

bleeding,  140. 

of  water,  44. 

Adaptation  a  necessary  feature  of 

cell  activity,  81. 

in  kidney,  106. 

Adrenalin,    effect   on    blood    com- 
position, 144. 

■ on   lymph,  pro- 
duction, 75. 
Adsorption,  10,  18,  32. 
Alcosol,  7. 

Alimentary  canal,  absorption  by,  44. 
Amino-acids,  19. 
Amphoteric  substances,  19. 
Ansemia,  139. 

effect  on  nutrition  of  ,148 . 

vessel  wall,  86. 

Anasarca,  62,  155. 


Angioneurotic  oedema,  176. 
Aorta,  effects  of  obstruction,  71. 
Appetite,   regulation   of    fluid   by, 

104. 
Arterial  pressure  in  plethora,  135. 
Ascites,  155. 
Ash  of  cells,  4. 
Assimilation  by  cell,  32. 

Bleeding,  beneficial  effects  of,  143. 

effects  of,  139. 

on  concentration  of 

blood,  94. 

on  lymph  produc- 

tion, 80. 

to  relieve  heart,  137. 


Blood,  changes  in  quantity  of,  134. 

composition   of,    after   adre- 

nalin, 75. 

concentration     in     Bright' s 

disease,  176. 

in     plethora, 

136. 

corpuscles,  behaviour  in  salt 

solutions,  29, 

dilution  of,   after  bleeding, 

140. 

estimations  in  finger,  63. 

formation,    effects    of    high 

altitudes  on,  145. 

plasma,  composition  of,  36. 

derived     from     sea- 

water,  36. 

jDressure,  effects  of  exercise  on, 

143. 

N    * 


180 


INDEX 


Blood  pressure,  effects  on  composi- 
tion of  blood, 
75. 

on  heart  of 

rise  in,  147. 

in  abdominal  capil- 

laries, 70. 

in  capillaries,  65. 

in  glomeruli,  108. 

influence  on   tissue 

fluid,  73. 

on  urinary 

secretion, 
110,  112. 


velocity  of,  in  plethora,  135, 

Blood-vessels,  absorption  by,  89,  95, 

99. 
Body  fluids,  36. 
Brain,  blood  supply  to,   135. 

influence  on  fluids  of  body, 

104. 
Bright's  disease,  154,  176. 


■Caffeine,  influence  on  kidney,  117, 

129. 
Oapillaries,  alteration  of  nutrition 
of,  7-3. 

relation  to  tissues,  99. 

■Capillary  j)ressure,  65. 

in       abdominal 

vessels,  70, 

in       glomeruli, 

109. 

in     relation     to 

osmotic  pres- 
sure, 101, 

unaltered  in  ve- 

nous obstruc- 
tion, 164, 

■ wall,  activity  of,  81, 

' alteration  after  ve- 
nous obstruction, 
17L 


Capillary  wall,  alterations    in,   in 
dropsy,  173. 

diffusion    through, 

67. 

influence  of  anaemia 

on,  86,  162. 

part       played       in 

dropsy,  160. 

structure  of,  65. 

Cell,  assimilation  by,  32. 

constituents,    how    originally 

determined,  37. 
contents,  osmotic  pressure  of, 

34. 

food  materials  in,  6. 

form  due  to  surface  tension,  6 , 

inorganic  constituents  of,  37. 

limiting  surface  of,  5. 

molecular  concentration,  3. 

surface,  lipoid  nature  of,  30. 

properties  of,  3. 

wall,  difference  from  Plasma- 

haut,  27, 
permeability  of,  23,  28. 


Cells,  activity  in  absorption,  57. 

form  of,  25. 

intestinal,  absorj)tion  by,  52. 

movement  of,  25. 

osmotic  energy  of,  2. 

relation  to  environment,  22. 

selective  power  of,  60. 

surface  of,  23. 

Cellulose,  28. 

Chemical     energy     of     cell     con- 
stituents, 3. 
factors  altering  distribu- 
tion of  body  fluid,  153. 

Chlorosis,  154. 

Circulation,   effects  of  venous  ob- 
struction, 169. 
through  kidneys,  133. 

Coefficient  of  partage,  33. 

Coelom,  35. 

Coelomic  fluid,  evolution  of,  36. 


INDEX 


181 


Coelomic  fluid,  regulation  of,  39. 
Colloidal  membranes,  permeability 
of,  66. 

solution,instability  of,  17. 

nature  of,  10. 

Colloids,  adsorption  in,  18. 

as  cell  constituents,  7. 

chemical   combination   of, 

19. 
^     definition  of,  7. 

determination  of  molecular 

weight,  11 — 13. 

electrical  charges  of,  17. 

imbibition  pressure  of,  15 

inertia  of,  20. 

molecular  weight  of,  11. 

size  of,  8. 

of  serum,  108. 

osmotic  jDressure  of,  11 — 

14. 
■ size  of  molecules,  10. 

surface  phenomena  of,  17, 

20. 
Compensatiou,  failure  of,  145,  165. 
Concentration ,  molecular,  of  cell,  3. 
Connective  tissue  spaces,  absorption 

from,  93. 
Convoluted  tubules,    secretion   in, 

124. 
Corpuscles,  red,  formation  of,  141. 
Crystalloids,  absorption  of,  90. 

effect  of  injection  on 

blood,  67. 

of  injection  on 

blood    ])res- 
sure,  78. 
passage  through  capil- 
lary wall,  67. 
Curare,   production    of    dropsy   in 

frog,  58. 
Cyanosis  in  heart  failure,  151. 
Cytoplasm,  molecular    weight     of 
constituents,  9. 
structure  of,  6. 


Dextrose,  effects  of  intravenous  in- 
jection, 76. 
Dialysis,  8. 
Diffusibility,  46. 
Diuresis,  114. 
Diuretics,  saline,  126. 
Diuretine,  129. 
Dropsy,  62. 

causation  of,  155 — 177. 

effects  of  salt-free  diet  on, 

154. 
in  heart  disease,  152. 

production     in      frog    by 

curare,  58. 

salt  deprivation  in,  129. 

Electrolytes,  17. 

adsorption  of,  18. 

Elephantiasis,  88,  177. 
Energy,  forms  of,  2. 

of  cell,  3. 

of    muscular    contraction, 

26. 

Environment,  modification  of,  by 
cell,  35. 

Excretion,  42, 

Exercise,  effects  on  blood  concen- 
tration, 143. 

Filtration  as  a  factor  in  absorption, 
98. 

hypothesis     of     lymph 

formation,  68. 
in  glomeruli,  108,  113. 

through  colloidal  mem- 

branes, 66. 
Fluid  balance  of  the  body,  134 — 
155. 

coelomic,  regulation  of,  39. 

intake  of,  41 — 61. 

of    body,    changes    in    total 

quantity  of,  134. 

of  tissues,  absorption  of,  88 

—103. 


182 


INDEX 


Muid,  output  of,  104—133. 

passage     of,    across    mem- 

branes, 45. 
Fluidity  of  protoplasm,  6. 
Pluids  of  body,  36. 
Food  materials  in  cell,  6. 
Foodstuffs,  combustion  of,  2. 
Frog,  kidneys  of,  121. 
Fucus,  ash  of,  4. 

Gammarus,  behaviour  in  salt  solu- 
tions, 31. 

*  Gel,'  definition  of,  7. 

Germination,  necessity  of  water 
for,  1. 

Globulins  of  serum,  19. 

Glomerular  transudate,  amount  of, 
132. 

Glomeruli,  circulation  through,  117. 

effect  of  plethora  on,  137. 

filtration  in,  108. 

functions  of,  107,  131. 

Granules,  secretory,  in  renal  tubules, 

123. 

Hsemoglobin,  osmotic  pressure  of, 

14. 
Haemolysis,  29. 
Heart  disease,  blood  pressure  in,  146. 

oedema  of,  165. 

failure,  145. 

by    over-distension, 

137. 

effects  on  circulation, 

147,  166. 

reaction  to  plethora,  135. 

to     rise     of     blood 

pressure,  147. 
Heidenhain's  theory  of  urinary  for- 
mation, 108. 
Hormones,  41. 
Hydraemia,  76. 

effects  on  capillary  wall, 

163. 


Hydrsemic  plethora,  44,  76,  137. 

as  a  result  of 

heart  failure, 
150. 

in      chlorosis, 

154. 

infiuence      on 

urinary  flow, 
114. 

produced     by 

injection    of 
crystalloids, 
68. 
Hydrosols,  7. 
Hydrothorax,  155. 

artificial    production 

of,  164. 
Hyperaemia,  effects  on  lymph  pro- 
duction, 72. 
Hypertrophy  of  heart  muscle,  148. 

Imbibition,  14. 

relation     to     chemical 

structure,  16. 
Inferior  vena  cava,  effects  of  ob- 
struction, 70. 
Inflammatory  oedema,  161,  174. 
Inorganic  salts  of  ceUs,  4. 

in  protoplasm,  37. 

Internal  media,  62. 

regulation  of,  41. 

Interstitial  fluid,  absorption  of,  88 

—103. 
Intestinal  cells,  mechanism  of  ab- 
sorption, 52. 
Intestine,  absorption  from,  49. 

of  serum  by, 

56. 
Intestines,  lymph  from,  69. 
Isotonic  fluids,  absorption  of,  93. 

Kidney,  dual  nature  of,  107. 

volume,  alteration  by  diu- 

retics, 115. 


INDEX 


183 


Kidneys,  action  of  hydrsemic  ple- 
thora oil,  139. 

circulation  through,  133. 

■ functions  of ,  42, 1 04— 1 33 

histological    changes   in, 

123. 
Kinetic  energy  of  cell,  3. 

Limbs,  lymph  production  in,  72. 
Lipoid  nature  of  cell  surface,  30. 
Liver,  alteration  by  lymphagogues, 
174. 

formation  of  lymph  iu,  84. 

function    as   safety   cistern, 

136. 

lymph,  69. 

pressure  in  capillaries  of,  65. 

Lud wig's  theory  of  urinary  forma- 
tion, 108. 

Lymph,  composition  of,  82. 

concentration  of,  in  dropsy, 

173. 

flow,  amount  of,  69. 

effects   of  muscular 

movements  on,  72. 

in  anaemia,  140. 

influence  of  plethora 

on,  l;;6. 

formation  by  vital  activity 

of  cells,  81. 

effects  of  nerves 

on,  175. 

. influence  of  ca- 

pillary    pres- 
sure on,  68. 

in    venous    ob- 

struction, 159. 

production  of,  62 — 87. 

relation  to  tissue  fluid,  64. 

Lymphagogues,  76,  83,  174. 
Lymphangiectasis,  88. 
Lymphatic  obstruction,  effects  of, 

177. 
Lymphatics,  64. 


Lymphatics,  effect  of  obstruction  of 
171. 

part  played  by  absorp- 

tion, 88. 

structure  of,  90. 

Martin's  fllter,  66. 
Mean  systemic  pressure,  165. 
Membranes,      colloidal,       passage 
through,  66. 

passage      of      fluid 

across,  45. 

permeability  of,  23. 

as  determin- 

ing osmotic 

pressure,  48. 

Metabolism  relating  to  solutions,  2. 

stimulating    effects   of 

diminished     oxygen 
tension  on,  142. 
Molecular  concentration  of   blood, 

67. 

of  plasma, 

106. 

of    urine, 

132. 
Mountain  air,  rejuvenating  effects 

of,  142. 
Muscle,  mechanism  of,  26. 

Narcosis,  effects  on  blood  concen- 
tration, 144. 

Nerve  propagation  a  surface 
phenomenon,  25. 

Nervous  oedema,  175. 

Normal  fluids,  definition  of,  3. 

Nussbaum's  experiment,  121. 

Nutritional  alterations  of  capillary 
v^all,  73. 

QEdema,  absorption  of  fluid  of,  95. 

condition  of  circulation  in, 

98. 

inflammatory,  174. 


184 


INDEX 


(Edema,  influence  of  sodium,  clilo- 
lide  on,  154. 

on    blood    flow, 

100. 

nervous,  ITo. 

of  heart  disease,  165. 


Osmometer,  12. 

Osmosis  as  factor  in  absorption  of 
tissue  fluid,  89. 

in    lympli    pro- 

duction, 82, 
Osmotic  energy  of  cells,  2. 

pressure    as    determining 

absorption,  46, 
51. 

dependence    on 

diffusibility, 
47. 

of  cell  contents, 

34. 

of  colloids,  11 — 

14. 

of  proteins,  101; 

108. 

of  urine,  118. 

relation sMps  of  cells,  27 — 

40. 
Output  of  fluid,  104—133. 

of  beart,  148. 

Oxidation  in  body,  2. 

Oxygen,  efiect  on  kidneys,  122. 

tension,    effects  of  dimi- 

nisbed,  141. 

Pericardium,  effects  of  ligature  of, 
167. 

injection  of  oil  into, 

146. 
Peritoneum,  absorption  from,  49. 
Permeability,  dependence  on  cbemi- 
cal  character,  24. 

irreciprocal,  54. 

of  frog's 

skin, 59. 


Permeability  of  capillaries  in  in- 
flammation, 161, 

of  cell  wall,  23,  28. 

of     colloidal     mem- 

branes, 66. 

of  membranes  as  de- 

termining osmotic 
pressure,  48. 

Phosphates,  secretion  by  kidneys, 
125. 

Plasma,  influence  of  composition  on 
urinary  secretion,  114. 

molecular  concentration  of, 

106. 

proteins  of,  76. 

FJasmahaut,  23,  27. 

changes  in,  33. 

permeability  of,  29. 

Plasmolysis,  29. 

Plethora,  134. 

effect  on  lymph  produc- 

tion, 75. 

hydrgeniic,  44,  76,  137. 

in  heart  disease,  151. 

not  necessary  for  produc- 

tion of  dropsy,  169. 

produced  by  CO  poison- 

ing, 142. 
Portal  vein,  effects  of  ligature,  70. 
Potential  energy  of  cell,  3. 
Production  of  IjTnph,  62 — 87. 
Proteins,  molecular  weight  of,  9. 

of  plasma,  76. 

osmotic  pressure  of,  9,  51, 

101,  108,  166. 
Protoplasm,    chemical    complexity 
of,  9. 

evolution  of,  1. 

fluidity  of,  6. 

lecithin  in,  30. 

permeability   of    sur- 

face layer,  30. 

physical  characters  of, 

2. 


INDEX 


185 


Protoplasm,    semi -permeability  of, 
29. 

structure  of,  5. 

surface  films  in,  22. 

layer   of,    27, 

28. 
Purgatives,  43,  60. 
Putrefaction,  necessity  of  water  for, 
1. 

QueUung,  14. 

Eed  corpuscles,  formation  of,  141. 

increased  formation 

in  heart  failure, 
151. 
Eenal  artery,  effects  of  clamping, 
116. 

dropsy,  176. 

portal  vein,  121. 

tubules,  functions  of,  121. 

influence  of,  118. 


Saline  dilute  tics,  126. 

Salt  deprivation  in  dropsy,  129. 

solutions,  absorption  of,  97. 

effect   of  injection. 


on     urinary 

flow,  106. 
Salts,  absorption  of,  in  alimentary 
canal,  43. 

as  diuretics,  114. 

inorganic,  of  cells,  4. 

of  protoplasm,  37. 

of  seaweeds,  4. 

of  serum,  4. 

physiological  significance  of, 

30. 

relative  absorption  of,  b'd. 

varying  absorption  of,  60. 

Sea-water,  changes  in  composition, 
o6. 


Sea-water,  modification  by  living 
organisms,  38. 

Seaweeds,  ash  of,  4. 

Secretion,  mechanism  of,  25. 

Secretory  functions  of  convoluted 
tubules,  123. 

granules,       hydrostatic 

pressure  in,  25. 

in  kidneys,  123. 

Semi-permeable  membranes,  11. 
Serous  cavities,  absorption  from,  90. 
Serum,     absorption     from    tissue 

spaces,  102. 

of,  55. 

antitryptic  action  of,  bo. 

globulins  of,  19. 

osmotic  pressure  of,  13, 101. 

of  proteins 

in,  66. 
Skin  of  frog,  absorption  by,  58. 
Soaps,  colloidal  condition  of,  8. 

osmotic  pressure  of,  14. 

Sodium  chloride,  absorption  of,  53. 

in  kid- 
neys, 126. 

in  urine,  106,  128. 

influence    in     in- 

creasing     body 
fluid,  153. 

influence  on  kid- 

ney, 116. 

permeability       of 

capillary  wall  to, 

67. 
*  Sol,'  definition  of,  7. 
Solution,  criteria  of,  11. 

relation  to  imbibition,  15. 

Stomach,  absorption  in,  44. 
Sugar,  excretion  by  kidney,  125. 

influence  on  kidnev,  116. 

Sugars,  absorption  of,  32,  60. 
Surface  energy  in  muscular  contrac- 
tion, 26. 

of  ceUs,  2. 


186 


INDEX 


Surface  films  of  colloids,  21. 

layer  of  protoplasm,  27. 

of  cell,  3,  23. 

phenoniena  of  colloids,  1*7. 

tension  as  cause  of  move- 

m.ent,  25. 

in  protoplasm,  6. 

pressure  exerted  by, 

24. 

Temperature  regulation,  42. 

Theocine,  129. 

Thoracic  duct,  origin  of  lymph  in, 

69. 
Thrombosis,  causation  of  oedema  by, 

158. 
Tissue  fluid,  62. 

absorption  of,  88 — 103. 

after  bleed- 

ing, 140. 

concentration    of,     in 

dropsy,  173. 

effect   of   exercise  on, 

143. 

investigation  of,  63. 


Tissues,  part  pla^^ed  by,  in  lymph 
formation,  82. 

specific  gravity  of,  63. 

Tongue,  oedema  of,  175. 
Tradescantia,  plasmolysis  in,  29. 
Transfusion,  134. 
Transudation  of  lymph,  67. 
Tubules  of  kidney,  functions  of,  118. 
Turgor  in  plants,  34. 

Tyndall  phenomenon  in  colloids,  10. 

Ultra-microscope,  10. 

Urea,  excretion  of,  121. 

Ureter,  effects  of  obstruction,  127. 

pressure,  110. 

Uric  acid,  excretion  of,  123. 


Urinary  secretion  inhydrsemia,  139 

in  plethora,  137. 

Urine,  composition  of,  112,  118. 

formation  of,  104 — 133. 

Urticaria    produced     by    lympha- 

gogues,  174. 

Yalve,  effects  of  damage  on  heart, 

148. 
Yaso-dilatation,  influence  on  pro- 
duction of  oedema, 
159. 
Vena  cava,  effects  of  obstruction  of, 

163. 
inferior,    effects   of   ob- 
struction of,  169. 
Yenous     congestion,     effects      on 
specific       gravity      of 
tissues,    73. 
obstruction,  Bolton's  me- 
thod of  pro- 
ducing, 163. 

dropsy  caused 

by,  158. 

effects    on 

lymph,  70. 

pressure  in  plethora,  135. 

influence  on  fail- 

ing heart,  150. 

pressures  after  venous  ob- 

struction, 164. 
Yilli,  absorption  by,  45. 
Yital    activity   as    explanation    of 
lymph  formation,  81. 

Water,  absorption  of,  44. 

excretion  of,  43,  106,  119. 

necessary  for  life,  1 . 

physical  characters  of,  1. 

regulation  of  intake,  43- 

Work  of  heart,  148. 

in  plethora,  135. 


BRADBURY,  AGNEW,  &  CO.  LD.,  PRINTERS,  LONDON  AND  TONBRIDGE. 
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